RARE DISEASE
Congenital herpes simplex virus infection
Congenital herpes simplex virus infection
Congenital herpes simplex virus infection
Synonyms: Antenatal herpes simplex virus infection, Mother-to-child transmission of herpes simplex virus infection
Synonyms: Antenatal herpes simplex virus infection, Mother-to-child transmission of herpes simplex virus infection
Synonyms: Antenatal herpes simplex virus infection, Mother-to-child transmission of herpes simplex virus infection
Drug discovery
1
drug
With orphan designation
Overview
Congenital herpes simplex virus (HSV) infection is a rare but severe neonatal condition caused by vertical transmission of HSV-1 or HSV-2 during pregnancy, delivery, or postnatally. Clinical manifestations range from localized skin, eye, or mouth (SEM) involvement to disseminated disease or central nervous system (CNS) infection, with risks of mortality and long-term neurodevelopmental impairment. Early diagnosis and prompt intravenous acyclovir therapy significantly improve outcomes.
Population
Incidence: ~10 cases per 100,000 births globally (~14,000 annual cases), with regional variability (higher in Africa due to HSV-2 prevalence; HSV-1 accounts for >60% of cases in the Americas and Europe) [6][10][16].
Highest risk: Infants born to mothers with primary HSV infection during the third trimester (33–50% transmission risk without suppressive therapy) [1][9].
Burden
Mortality: Up to 60% untreated; reduced to 4% (CNS) and 30% (disseminated) with early antiviral therapy [3][7].
Morbidity: Neurologic sequelae (e.g., seizures, developmental delay) in 15–30% of survivors; SEM disease rarely progresses if treated promptly [5][7][16].
Global Impact: Disproportionately affects low-resource regions due to delayed diagnosis and limited access to antivirals, contributing to long-term disability and healthcare costs [6][17].
Key interventions include maternal screening, clinician awareness of nonspecific neonatal symptoms (e.g., sepsis-like presentation), and rapid PCR testing of CSF/skin lesions [5][9].
Therapies
High-dose IV acyclovir (60 mg/kg/day for 14–21 days) based on disease severity (SEM: 14 days; CNS/disseminated: 21 days) [3][7][16].
Oral acyclovir suppressive therapy (6 months post-IV) to reduce recurrence and improve neurodevelopmental outcomes in CNS cases [7][14].
Cesarean delivery for active maternal genital lesions and maternal antiviral prophylaxis (e.g., valacyclovir) during late pregnancy to reduce viral shedding [7][9].
Categories: rare developmental anomalies during embryogenesis, rare infectious diseases, rare teratologic disorders
Research Papers
105 drug discovery papers about Congenital herpes simplex virus infection, with 1 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
105 drug discovery papers about Congenital herpes simplex virus infection, with 1 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
antibodies
2025-07-23 | Management of neonates born to mothers with active genital herpes simplex virus infection: an alternative approach.
Although considered a rare disease, neonatal HSV infection represents a disease in urgent need of preventive strategies, as it results in substantial neonatal morbidity and mortality. This review summarizes its current epidemiology and discusses guidances on the management of the asymptomatic neonate born to mothers with active genital HSV infection. Timely detection and early high-dose acyclovir treatment of neonatal HSV infection decreases mortality. All neonates born to mothers with active genital HSV infection in the third trimester or at delivery should be tested for HSV infection. The newborn management has depended on whether the mother has experienced a primary or recurrent genital HSV infection based on maternal serologic testing and PCR testing of the genital lesion. An alternative strategy on neonatal management is proposed that is based on type of maternal HSV infection and perinatal risk factors. The incidence of neonatal HSV infection is increasing with more infections due to HSV-1 than HSV-2. Guidances addressing management of the asymptomatic newborn exposed to active maternal genital HSV infection are discussed.
2022-08-29 | Monoclonal antibody therapy of herpes simplex virus: An opportunity to decrease congenital and perinatal infections.
The fetal/neonatal period represents both a unique window of opportunity for interventions as well as vulnerability to a number of viral infections. While Herpesviruses such as herpes simplex virus (HSV) are highly prevalent and typically of little consequence among healthy adults, they are among the most consequential infections of early life. Despite treatment with antiviral drugs, neonatal HSV (nHSV) infections can still result in significant mortality and lifelong neurological morbidity. Fortunately, newborns in our pathogen-rich world inherit some of the protection provided by the maternal immune system in the form of transferred antibodies. Maternal seropositivity, resulting in placental transfer of antibodies capable of neutralizing virus and eliciting the diverse effector functions of the innate immune system are associated with dramatically decreased risk of nHSV. Given this clear epidemiological evidence of reduced risk of infection and its sequelae, we present what is known about the ability of monoclonal antibody therapies to treat or prevent HSV infection and explore how effective antibody-based interventions in conjunction with antiviral therapy might reduce early life mortality and long-term morbidity.
2020-06-04 | High level antibodies to TORCH in the IVIG preparation from Taiwanese.
Congenital TORCH (toxoplasmosis, other viruses [varicella-zoster virus, VZV, etc.], rubella, cytomegalovirus [CMV], Herpes simplex virus [HSV]) infections are major causes of prenatal, perinatal, and postnatal morbidity and mortality. Although treatment or prevention strategies are available for these pathogens, all drugs may not be safe during the pregnancy. The aim of this study is to measure the antibodies (Abs) concentration in the intravenous immunoglobulin (IVIG) preparation to evaluate the therapeutic potential for TORCH infection. We tested the only one commercial IVIG preparation from Taiwanese for the presence of Abs against Toxoplasma gondii, VZV, Epstein-Barr virus (EBV), measles, mumps, rubella, CMV, HSV type 1 (HSV-1), and HSV type 2 (HSV-2) by using enzyme-linked immunosorbent assay or chemiluminescent microparticle immunoassay. In our study, the median level (range) of anti-CMV immunoglobulin G (IgG) is > 250 (All > 250) (arbitrary unit, AU)/mL, anti-EBV > 200 (All > 200) (relative unit, RU)/mL, anti-HSV > 200 (152.75 to >200) RU/mL, anti-VZV > 5000 (All > 5000) IU/L, anti-measles > 5000 (All > 5000) IU/L, anti-mumps > 200 (156.5 to > 200) RU/mL, anti-rubella 209.8 IU/mL (192.7 to 238.5), and anti-Toxoplasma is 14.05 (12.3 to 16) IU/mL. There was not any immunoglobulin M (IgM) against HSV, VZV, mumps, measles, rubella, CMV, EBV, and Toxoplasma in the "Taiwan Blood Services Foundation" IVIG preparations. There was high activity against T. gondii, VZV, EBV, measles, mumps, rubella, CMV, HSV-1, and HSV-2 in all IVIG batches. Further investigation is warranted to confirm the efficacy of IVIG from Taiwanese for congenital TORCH infections.
2019-09-24 | Detection of antibody-secreting cells specific for the cytomegalovirus and herpes simplex virus surface antigens.
Infections with the herpes simplex virus (HSV) and the human cytomegalovirus (HCMV) can lead to life-threatening diseases, particularly in immunosuppressed patients. Furthermore, HSV infections at birth (herpes neonatorum) can result in a disseminated disease associated with a fatal multiorgan failure. Congenital HCMV infections can result in miscarriage, serious birth defects or developmental disabilities. Antibody-based interventions with hyperimmunoglobulins showed encouraging results in clinical studies, but clearly need to be improved. The isolation of highly neutralizing monoclonal antibodies is a promising strategy to establish potent therapy options against HSV and HCMV infections. Monoclonal antibodies are commonly isolated from hybridomas or EBV-immortalized B-cell clones. The screening procedure to identify virus-specific cells from a cell mixture is a challenging step, since most of the highly neutralizing antibodies target complex conformational epitopes on the virus surface. Conventional assays such as ELISA are based on purified viral proteins and inappropriate to display complex epitopes. To overcome this obstacle, we have established two full-virus based methods that allow screening for cells and antibodies targeting complex conformational epitopes on viral surface antigens. The methods are suitable to detect surface antigen-specific cells from a cell mixture and may facilitate the isolation of highly neutralizing antibodies against HSV and HCMV.
2018-03-20 | Maternal Antiviral Immunoglobulin Accumulates in Neural Tissue of Neonates To Prevent HSV Neurological Disease.
While antibody responses to neurovirulent pathogens are critical for clearance, the extent to which antibodies access the nervous system to ameliorate infection is poorly understood. In this study on herpes simplex virus 1 (HSV-1), we demonstrate that HSV-specific antibodies are present during HSV-1 latency in the nervous systems of both mice and humans. We show that antibody-secreting cells entered the trigeminal ganglion (TG), a key site of HSV infection, and persisted long after the establishment of latent infection. We also demonstrate the ability of passively administered IgG to enter the TG independently of infection, showing that the naive TG is accessible to antibodies. The translational implication of this finding is that human fetal neural tissue could contain HSV-specific maternally derived antibodies. Exploring this possibility, we observed HSV-specific IgG in HSV DNA-negative human fetal TG, suggesting passive transfer of maternal immunity into the prenatal nervous system. To further investigate the role of maternal antibodies in the neonatal nervous system, we established a murine model to demonstrate that maternal IgG can access and persist in neonatal TG. This maternal antibody not only prevented disseminated infection but also completely protected the neonate from neurological disease and death following HSV challenge. Maternal antibodies therefore have a potent protective role in the neonatal nervous system against HSV infection. These findings strongly support the concept that prevention of prenatal and neonatal neurotropic infections can be achieved through maternal immunization.IMPORTANCE Herpes simplex virus 1 is a common infection of the nervous system that causes devastating neonatal disease. Using mouse and human tissue, we discovered that antiviral antibodies accumulate in neural tissue after HSV-1 infection in adults. Similarly, these antibodies pass to the offspring during pregnancy. We found that antiviral maternal antibodies can readily access neural tissue of the fetus and neonate. These maternal antibodies then protect neonatal mice against HSV-1 neurological infection and death. These results underscore the previously unappreciated role of maternal antibodies in protecting fetal and newborn nervous systems against infection. These data suggest that maternal immunization would be efficacious at preventing fetal/neonatal neurological infections.
small molecules
2026-07-25 | HSV, HIV, and Pregnancy: Epidemiology, Viral Interactions, Management, and Prevention.
We summarize the epidemiology, biology, management and prevention of HSV-2 and HIV in pregnancy. The seroprevalence of HSV-2 is higher in people living with HIV than in HIV-negative people, and 75% of women with recurrent genital herpes may have a recurrence during pregnancy. Those with a history of recurrent genital HSV infection should be offered acyclovir/valacyclovir at 36 weeks gestation to decrease need for C-section. The most important intervention for reducing HIV vertical transmission is maternal antiretroviral therapy (ART) to suppress HIV replication. Maternal ART also reduces HSV-2 cervicovaginal shedding and thus, HSV-2 vertical transmission. HSV-2 viral shedding is incompletely suppressed with acyclovir/valacyclovir, and newer drugs such as the helicase-primase inhibitors show promise but have not been studied in pregnancy. Safe options also exist for preventing HIV acquisition in pregnancy but remain in development for HSV-2. Safe, effective HSV-2/HIV management strategies exist in pregnancy.
2026-04-28 | Cyclic GMP-AMP Synthase (cGAS) Activators for Congenital Herpes Prevention
UniProt identifies cGAS (Q8N884) as key innate immune receptor sensing viral nucleic acids and producing type I interferons. The protein catalyzes cyclic GMP-AMP formation from ATP and GTP, triggering antiviral responses. Enhancing cGAS activity could prevent vertical transmission of herpes simplex virus from mother to newborn, addressing the devastating congenital herpes infections described in Orphanet (ORDO:293).
2026-04-01 | Chorioretinitis Scarring in a Neonate Secondary to Congenital Herpes Simplex Type 2.
Purpose: To describe a rare case of congenital herpes simplex virus type 2 (HSV-2) infection with bilateral retinal involvement in a neonate. Methods: A single case is presented along with a brief literature review. Results: A neonate born to a mother with unrecognized HSV-2 infection presented with skin lesions initially thought to be secondary to amniotic band syndrome. Subsequent evaluation revealed positive skin cultures for HSV-2, suggesting in utero transmission, most likely during the early second trimester. Fundus examination demonstrated large, bilateral hyperpigmented chorioretinal scars consistent with retinal involvement. Conclusions: Congenital HSV infection, although rare, should be considered in neonates presenting with skin lesions and chorioretinitis. Early recognition and prompt initiation of intravenous acyclovir therapy, even before culture confirmation when clinical suspicion is high, are critical to optimize outcomes.
2025-10-09 | Herpes simplex virus - state of the art of prevention and treatment.
Neonatal herpes simplex virus (HSV) infection remains a life-threatening condition with high morbidity and mortality despite advances in diagnostics and therapy. Transmission occurs predominantly during delivery and the three main clinical phenotypes; skin-eye-mouth disease, central nervous system disease, and disseminated disease, carry distinct prognoses. This state-of-the-art review focuses on prevention and consideration of empirical treatment. Maternal antiviral prophylaxis in late pregnancy has shown to reduce the frequency of active HSV outbreaks at delivery. Decisions on empirical acyclovir therapy must balance early recognition against overtreatment, guided by the number needed to treat, which in European settings among term and near-term infants ranges from over 1,000 for early-onset sepsis to ∼150 for late-onset sepsis. Ongoing research focuses on preventive strategies, including vaccine development and novel biomarkers on dried blood spot samples to improve outcomes.
2025-09-12 | USP18 Deficiency Presenting as Severe Neonatal Encephalopathy: A Case Report and Review of Pseudo-TORCH Syndromes.
Pseudo-TORCH (Toxoplasma, "Other" agents, Rubella, Cytomegalovirus, Herpes simplex, etc.) syndromes are rare genetic disorders that mimic congenital TORCH infections but lack an infectious cause. Affected infants present with encephalopathy, intracranial calcifications, and congenital anomalies. We report a term male infant who developed catastrophic encephalopathy and coagulopathy on day eight of life, with neuroimaging showing hemorrhages, calcifications, and cortical malformations. Whole-exome sequencing revealed a homozygous splice-site mutation in USP18, confirming pseudo-TORCH syndrome type 2. Despite maximal intensive care, the infant succumbed at one month of age. This case illustrates the diagnostic challenges and rapid progression of USP18 deficiency, highlights the value of early genetic confirmation for family counseling, and reviews the spectrum of pseudo-TORCH syndromes. Emerging therapies targeting interferon pathways may offer future hope. Our literature review highlights the differential diagnoses and genetic variability among pseudo-TORCH conditions, which include mutations in OCLN, USP18, STAT2, and JAM3. This emphasizes the importance of early genetic confirmation for better prognosis and family counseling. Emerging therapies targeting the interferon pathway, such as Janus kinase (JAK) inhibitors, are currently under investigation and may offer hope for these previously untreatable disorders. This case underscores the necessity of considering pseudo-TORCH syndromes in neonates who present with unexplained encephalopathy and brain calcifications after infectious causes have been ruled out.
proteins
2023-04-04 | Investigating the Safety and Efficacy of the Synthetic Drug Herbix on Immune Responses Involved in the Treatment of a Mouse Model of Herpes Simplex Virus.
Herpes simplex virus-1 (HSV-1) infections can cause significant harm to individuals, including blindness, congenital defects, genital herpes, and even cancer, with no definitive cure .so, finding new treatment strategies is crucial. In this study, 25 male BALB/c mice were used to conduct a mouse model of herpes by subcutaneously injecting an HSV-1 suspension (100 µL of 1× PFU/mL). The mice were divided into 5 groups with groups 1 to 3 designated as intervention groups, and groups 4 and 5 serving as positive and negative control groups, respectively. After 2 days of virus inoculation, the mice were treated with different concentrations of Herbix (100, 200, and 300 mg/mL) via subcutaneous injection. Mice Blood samples (0.5 to 1 mL) were taken from the mice before and after the experiments, and after three-week follow-up period, the mice were sacrificed and the spleens were removed for lymphocyte analysis. we found that administration of Herbix at a dose of 300 mg/mL showed the greatest efficacy, characterized by a delay in skin lesion formation, an increment in survival rate and lymphocyte proliferation, upregulation of the gene expression of interferon alpha (IFN-α) and tumor necrosis factor alpha (TNF-α), and an increase in the polarization of cytotoxic and helper T lymphocytes compared to the control group. These results suggest that Herbix at a dose of 300 mg/mL is effective in treating murine herpes and stimulating immune responses, making it a potential candidate for further investigation as an antiherpetic drug.
2016-04-18 | Novel heparan sulfate-binding peptides for blocking herpesvirus entry.
Human cytomegalovirus (HCMV) infection can lead to congenital hearing loss and mental retardation. Upon immune suppression, reactivation of latent HCMV or primary infection increases morbidity in cancer, transplantation, and late stage AIDS patients. Current treatments include nucleoside analogues, which have significant toxicities limiting their usefulness. In this study we screened a panel of synthetic heparin-binding peptides for their ability to prevent CMV infection in vitro. A peptide designated, p5+14 exhibited ~ 90% reduction in murine CMV (MCMV) infection. Because negatively charged, cell-surface heparan sulfate proteoglycans (HSPGs), serve as the attachment receptor during the adsorption phase of the CMV infection cycle, we hypothesized that p5+14 effectively competes for CMV adsorption to the cell surface resulting in the reduction in infection. Positively charged Lys residues were required for peptide binding to cell-surface HSPGs and reducing viral infection. We show that this inhibition was not due to a direct neutralizing effect on the virus itself and that the peptide blocked adsorption of the virus. The peptide also inhibited infection of other herpesviruses: HCMV and herpes simplex virus 1 and 2 in vitro, demonstrating it has broad-spectrum antiviral activity. Therefore, this peptide may offer an adjunct therapy for the treatment of herpes viral infections and other viruses that use HSPGs for entry.
gene therapies
2026-07-24 | Comparative Genomics of Herpes Simplex Virus 2 Isolated from a Maternal-Neonatal Dyad Reveals High Consensus Sequence Homology as Well as Minor Variant Diversity.
Neonatal herpes simplex virus disease most often occurs following mother-to-neonate transmission during childbirth. However, genomic differences between the maternal and neonatal viral populations are poorly understood. Here, we performed deep whole-genome sequencing of clinical HSV-2 samples obtained from a maternal-neonatal dyad to investigate viral population dynamics during transmission.
2026-04-14 | TORCH: Current state of knowledge as of 2025.
The acronym TORCH designates a group of pathogens that can lead to serious pregnancy complications, such as miscarriage, fetal growth restriction, and congenital infections. This review summarizes current insights into these infections, offering practical guidance primarily for obstetricians, infectious disease specialists, and general practitioners involved in prenatal care. The TORCH complex includes Toxoplasma gondii, Rubella virus, Cytomegalovirus (CMV), and Herpes simplex virus (HSV). The definition may be extended to encompass additional (other) pathogens such as Hepatitis B and C viruses (HBV, HCV), Human immunodeficiency virus (HIV), Varicella-zoster virus (VZV), Treponema pallidum (syphilis), Parvovirus B19, and Zika virus. Screening practices for TORCH infections during pregnancy vary significantly across countries. Despite widespread access to medical care and increasing awareness among women planning pregnancy, routine screening for TORCH pathogens is not universally implemented. In Poland, diagnostic procedures during pregnancy are defined by the Standard of Perinatal Care established by the Ministry of Health. This regulation- which replaced earlier recommendations of the Polish Society of Gynecologists and Obstetricians- does not distinguish between ,,mandatory" and ,,recommended" tests but specifies a unified set of investigations to be performed at defined stages of pregnancy. Screening conducted during pregnancy plays a crucial role in detecting previously unrecognized infections. In Poland , a substantial proportion of new diagnoses of HIV, HBV and HCV among young women are made during routine antenatal testing, underscoring the importance of standardized serological screening in prenatal care rather than relying on diagnosis before conception. However, due to their distinct epidemiological and clinical profiles, HIV, HBV, and HCV infections are not discussed in detail in this review.
2021-10-25 | [The role of herpesviruses in development of diseases of the urogenital tract and infertility in women].
This review presents the data on the spreading of all known human herpesviruses (НHVs) in female urogenital tract. According to the WHO almost 500 million people worldwide suffer from genital infection caused by НHVs. НHVs were detected in various inflammatory diseases of female upper and lower genital tract (vaginitis and cervicitis), in extrauterine pregnancy (in fallopian tubes), in infertility (cervical channel, endometrium and ovaries). Herpes simplex virus 1 (HSV‑1) was identified for the first time in oocytes after failed in vitro fertilization (IVF). НHVs produce negative effect on the entire reproductive process from conception to childbirth. It was established that HSV, cytomegalovirus (CMV) and human herpesvirus 6 (HHV-6) markedly increase the risk of spontaneous abortion, preterm birth and stillbirth. Intrauterine НHV infection is a major cause of congenital malformations. Data on humoral and cell immunity in genital herpesvirus infections (НHVI) are also reviewed. Intravaginal HSV‑2 infection changes cell composition of vaginal mucosa, i.e., together with cells mobilized from the blood, protective role is performed by resident memory T‑cells (TRM), natural killer cells (NK‑cells) and regulatory T‑cells (Treg) whose function consists in maintaining the balance of the activities of lymphocytes. Constant НHVI spreading is largely explained by transition of primary infection to potentially reactivating latent form, since latent virus is unavailable to immune recognition and medicines. The genome editing system CRISPR/Cas9 can recognize and modify not only active but also latent viruses. The promising pilot results with the use of this system offer the possibility of developing innovative technologies for НHV elimination and НHVI eradication.
2017-06-02 | CRISPR/Cas9-Mediated Genome Editing of Herpesviruses Limits Productive and Latent Infections.
Herpesviruses infect the majority of the human population and can cause significant morbidity and mortality. Herpes simplex virus (HSV) type 1 causes cold sores and herpes simplex keratitis, whereas HSV-2 is responsible for genital herpes. Human cytomegalovirus (HCMV) is the most common viral cause of congenital defects and is responsible for serious disease in immuno-compromised individuals. Epstein-Barr virus (EBV) is associated with infectious mononucleosis and a broad range of malignancies, including Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's disease, and post-transplant lymphomas. Herpesviruses persist in their host for life by establishing a latent infection that is interrupted by periodic reactivation events during which replication occurs. Current antiviral drug treatments target the clinical manifestations of this productive stage, but they are ineffective at eliminating these viruses from the infected host. Here, we set out to combat both productive and latent herpesvirus infections by exploiting the CRISPR/Cas9 system to target viral genetic elements important for virus fitness. We show effective abrogation of HCMV and HSV-1 replication by targeting gRNAs to essential viral genes. Simultaneous targeting of HSV-1 with multiple gRNAs completely abolished the production of infectious particles from human cells. Using the same approach, EBV can be almost completely cleared from latently infected EBV-transformed human tumor cells. Our studies indicate that the CRISPR/Cas9 system can be effectively targeted to herpesvirus genomes as a potent prophylactic and therapeutic anti-viral strategy that may be used to impair viral replication and clear latent virus infection.
antibodies
2025-07-23 | Management of neonates born to mothers with active genital herpes simplex virus infection: an alternative approach.
Although considered a rare disease, neonatal HSV infection represents a disease in urgent need of preventive strategies, as it results in substantial neonatal morbidity and mortality. This review summarizes its current epidemiology and discusses guidances on the management of the asymptomatic neonate born to mothers with active genital HSV infection. Timely detection and early high-dose acyclovir treatment of neonatal HSV infection decreases mortality. All neonates born to mothers with active genital HSV infection in the third trimester or at delivery should be tested for HSV infection. The newborn management has depended on whether the mother has experienced a primary or recurrent genital HSV infection based on maternal serologic testing and PCR testing of the genital lesion. An alternative strategy on neonatal management is proposed that is based on type of maternal HSV infection and perinatal risk factors. The incidence of neonatal HSV infection is increasing with more infections due to HSV-1 than HSV-2. Guidances addressing management of the asymptomatic newborn exposed to active maternal genital HSV infection are discussed.
2022-08-29 | Monoclonal antibody therapy of herpes simplex virus: An opportunity to decrease congenital and perinatal infections.
The fetal/neonatal period represents both a unique window of opportunity for interventions as well as vulnerability to a number of viral infections. While Herpesviruses such as herpes simplex virus (HSV) are highly prevalent and typically of little consequence among healthy adults, they are among the most consequential infections of early life. Despite treatment with antiviral drugs, neonatal HSV (nHSV) infections can still result in significant mortality and lifelong neurological morbidity. Fortunately, newborns in our pathogen-rich world inherit some of the protection provided by the maternal immune system in the form of transferred antibodies. Maternal seropositivity, resulting in placental transfer of antibodies capable of neutralizing virus and eliciting the diverse effector functions of the innate immune system are associated with dramatically decreased risk of nHSV. Given this clear epidemiological evidence of reduced risk of infection and its sequelae, we present what is known about the ability of monoclonal antibody therapies to treat or prevent HSV infection and explore how effective antibody-based interventions in conjunction with antiviral therapy might reduce early life mortality and long-term morbidity.
2020-06-04 | High level antibodies to TORCH in the IVIG preparation from Taiwanese.
Congenital TORCH (toxoplasmosis, other viruses [varicella-zoster virus, VZV, etc.], rubella, cytomegalovirus [CMV], Herpes simplex virus [HSV]) infections are major causes of prenatal, perinatal, and postnatal morbidity and mortality. Although treatment or prevention strategies are available for these pathogens, all drugs may not be safe during the pregnancy. The aim of this study is to measure the antibodies (Abs) concentration in the intravenous immunoglobulin (IVIG) preparation to evaluate the therapeutic potential for TORCH infection. We tested the only one commercial IVIG preparation from Taiwanese for the presence of Abs against Toxoplasma gondii, VZV, Epstein-Barr virus (EBV), measles, mumps, rubella, CMV, HSV type 1 (HSV-1), and HSV type 2 (HSV-2) by using enzyme-linked immunosorbent assay or chemiluminescent microparticle immunoassay. In our study, the median level (range) of anti-CMV immunoglobulin G (IgG) is > 250 (All > 250) (arbitrary unit, AU)/mL, anti-EBV > 200 (All > 200) (relative unit, RU)/mL, anti-HSV > 200 (152.75 to >200) RU/mL, anti-VZV > 5000 (All > 5000) IU/L, anti-measles > 5000 (All > 5000) IU/L, anti-mumps > 200 (156.5 to > 200) RU/mL, anti-rubella 209.8 IU/mL (192.7 to 238.5), and anti-Toxoplasma is 14.05 (12.3 to 16) IU/mL. There was not any immunoglobulin M (IgM) against HSV, VZV, mumps, measles, rubella, CMV, EBV, and Toxoplasma in the "Taiwan Blood Services Foundation" IVIG preparations. There was high activity against T. gondii, VZV, EBV, measles, mumps, rubella, CMV, HSV-1, and HSV-2 in all IVIG batches. Further investigation is warranted to confirm the efficacy of IVIG from Taiwanese for congenital TORCH infections.
2019-09-24 | Detection of antibody-secreting cells specific for the cytomegalovirus and herpes simplex virus surface antigens.
Infections with the herpes simplex virus (HSV) and the human cytomegalovirus (HCMV) can lead to life-threatening diseases, particularly in immunosuppressed patients. Furthermore, HSV infections at birth (herpes neonatorum) can result in a disseminated disease associated with a fatal multiorgan failure. Congenital HCMV infections can result in miscarriage, serious birth defects or developmental disabilities. Antibody-based interventions with hyperimmunoglobulins showed encouraging results in clinical studies, but clearly need to be improved. The isolation of highly neutralizing monoclonal antibodies is a promising strategy to establish potent therapy options against HSV and HCMV infections. Monoclonal antibodies are commonly isolated from hybridomas or EBV-immortalized B-cell clones. The screening procedure to identify virus-specific cells from a cell mixture is a challenging step, since most of the highly neutralizing antibodies target complex conformational epitopes on the virus surface. Conventional assays such as ELISA are based on purified viral proteins and inappropriate to display complex epitopes. To overcome this obstacle, we have established two full-virus based methods that allow screening for cells and antibodies targeting complex conformational epitopes on viral surface antigens. The methods are suitable to detect surface antigen-specific cells from a cell mixture and may facilitate the isolation of highly neutralizing antibodies against HSV and HCMV.
2018-03-20 | Maternal Antiviral Immunoglobulin Accumulates in Neural Tissue of Neonates To Prevent HSV Neurological Disease.
While antibody responses to neurovirulent pathogens are critical for clearance, the extent to which antibodies access the nervous system to ameliorate infection is poorly understood. In this study on herpes simplex virus 1 (HSV-1), we demonstrate that HSV-specific antibodies are present during HSV-1 latency in the nervous systems of both mice and humans. We show that antibody-secreting cells entered the trigeminal ganglion (TG), a key site of HSV infection, and persisted long after the establishment of latent infection. We also demonstrate the ability of passively administered IgG to enter the TG independently of infection, showing that the naive TG is accessible to antibodies. The translational implication of this finding is that human fetal neural tissue could contain HSV-specific maternally derived antibodies. Exploring this possibility, we observed HSV-specific IgG in HSV DNA-negative human fetal TG, suggesting passive transfer of maternal immunity into the prenatal nervous system. To further investigate the role of maternal antibodies in the neonatal nervous system, we established a murine model to demonstrate that maternal IgG can access and persist in neonatal TG. This maternal antibody not only prevented disseminated infection but also completely protected the neonate from neurological disease and death following HSV challenge. Maternal antibodies therefore have a potent protective role in the neonatal nervous system against HSV infection. These findings strongly support the concept that prevention of prenatal and neonatal neurotropic infections can be achieved through maternal immunization.IMPORTANCE Herpes simplex virus 1 is a common infection of the nervous system that causes devastating neonatal disease. Using mouse and human tissue, we discovered that antiviral antibodies accumulate in neural tissue after HSV-1 infection in adults. Similarly, these antibodies pass to the offspring during pregnancy. We found that antiviral maternal antibodies can readily access neural tissue of the fetus and neonate. These maternal antibodies then protect neonatal mice against HSV-1 neurological infection and death. These results underscore the previously unappreciated role of maternal antibodies in protecting fetal and newborn nervous systems against infection. These data suggest that maternal immunization would be efficacious at preventing fetal/neonatal neurological infections.
small molecules
2026-07-25 | HSV, HIV, and Pregnancy: Epidemiology, Viral Interactions, Management, and Prevention.
We summarize the epidemiology, biology, management and prevention of HSV-2 and HIV in pregnancy. The seroprevalence of HSV-2 is higher in people living with HIV than in HIV-negative people, and 75% of women with recurrent genital herpes may have a recurrence during pregnancy. Those with a history of recurrent genital HSV infection should be offered acyclovir/valacyclovir at 36 weeks gestation to decrease need for C-section. The most important intervention for reducing HIV vertical transmission is maternal antiretroviral therapy (ART) to suppress HIV replication. Maternal ART also reduces HSV-2 cervicovaginal shedding and thus, HSV-2 vertical transmission. HSV-2 viral shedding is incompletely suppressed with acyclovir/valacyclovir, and newer drugs such as the helicase-primase inhibitors show promise but have not been studied in pregnancy. Safe options also exist for preventing HIV acquisition in pregnancy but remain in development for HSV-2. Safe, effective HSV-2/HIV management strategies exist in pregnancy.
2026-04-28 | Cyclic GMP-AMP Synthase (cGAS) Activators for Congenital Herpes Prevention
UniProt identifies cGAS (Q8N884) as key innate immune receptor sensing viral nucleic acids and producing type I interferons. The protein catalyzes cyclic GMP-AMP formation from ATP and GTP, triggering antiviral responses. Enhancing cGAS activity could prevent vertical transmission of herpes simplex virus from mother to newborn, addressing the devastating congenital herpes infections described in Orphanet (ORDO:293).
2026-04-01 | Chorioretinitis Scarring in a Neonate Secondary to Congenital Herpes Simplex Type 2.
Purpose: To describe a rare case of congenital herpes simplex virus type 2 (HSV-2) infection with bilateral retinal involvement in a neonate. Methods: A single case is presented along with a brief literature review. Results: A neonate born to a mother with unrecognized HSV-2 infection presented with skin lesions initially thought to be secondary to amniotic band syndrome. Subsequent evaluation revealed positive skin cultures for HSV-2, suggesting in utero transmission, most likely during the early second trimester. Fundus examination demonstrated large, bilateral hyperpigmented chorioretinal scars consistent with retinal involvement. Conclusions: Congenital HSV infection, although rare, should be considered in neonates presenting with skin lesions and chorioretinitis. Early recognition and prompt initiation of intravenous acyclovir therapy, even before culture confirmation when clinical suspicion is high, are critical to optimize outcomes.
2025-10-09 | Herpes simplex virus - state of the art of prevention and treatment.
Neonatal herpes simplex virus (HSV) infection remains a life-threatening condition with high morbidity and mortality despite advances in diagnostics and therapy. Transmission occurs predominantly during delivery and the three main clinical phenotypes; skin-eye-mouth disease, central nervous system disease, and disseminated disease, carry distinct prognoses. This state-of-the-art review focuses on prevention and consideration of empirical treatment. Maternal antiviral prophylaxis in late pregnancy has shown to reduce the frequency of active HSV outbreaks at delivery. Decisions on empirical acyclovir therapy must balance early recognition against overtreatment, guided by the number needed to treat, which in European settings among term and near-term infants ranges from over 1,000 for early-onset sepsis to ∼150 for late-onset sepsis. Ongoing research focuses on preventive strategies, including vaccine development and novel biomarkers on dried blood spot samples to improve outcomes.
2025-09-12 | USP18 Deficiency Presenting as Severe Neonatal Encephalopathy: A Case Report and Review of Pseudo-TORCH Syndromes.
Pseudo-TORCH (Toxoplasma, "Other" agents, Rubella, Cytomegalovirus, Herpes simplex, etc.) syndromes are rare genetic disorders that mimic congenital TORCH infections but lack an infectious cause. Affected infants present with encephalopathy, intracranial calcifications, and congenital anomalies. We report a term male infant who developed catastrophic encephalopathy and coagulopathy on day eight of life, with neuroimaging showing hemorrhages, calcifications, and cortical malformations. Whole-exome sequencing revealed a homozygous splice-site mutation in USP18, confirming pseudo-TORCH syndrome type 2. Despite maximal intensive care, the infant succumbed at one month of age. This case illustrates the diagnostic challenges and rapid progression of USP18 deficiency, highlights the value of early genetic confirmation for family counseling, and reviews the spectrum of pseudo-TORCH syndromes. Emerging therapies targeting interferon pathways may offer future hope. Our literature review highlights the differential diagnoses and genetic variability among pseudo-TORCH conditions, which include mutations in OCLN, USP18, STAT2, and JAM3. This emphasizes the importance of early genetic confirmation for better prognosis and family counseling. Emerging therapies targeting the interferon pathway, such as Janus kinase (JAK) inhibitors, are currently under investigation and may offer hope for these previously untreatable disorders. This case underscores the necessity of considering pseudo-TORCH syndromes in neonates who present with unexplained encephalopathy and brain calcifications after infectious causes have been ruled out.
proteins
2023-04-04 | Investigating the Safety and Efficacy of the Synthetic Drug Herbix on Immune Responses Involved in the Treatment of a Mouse Model of Herpes Simplex Virus.
Herpes simplex virus-1 (HSV-1) infections can cause significant harm to individuals, including blindness, congenital defects, genital herpes, and even cancer, with no definitive cure .so, finding new treatment strategies is crucial. In this study, 25 male BALB/c mice were used to conduct a mouse model of herpes by subcutaneously injecting an HSV-1 suspension (100 µL of 1× PFU/mL). The mice were divided into 5 groups with groups 1 to 3 designated as intervention groups, and groups 4 and 5 serving as positive and negative control groups, respectively. After 2 days of virus inoculation, the mice were treated with different concentrations of Herbix (100, 200, and 300 mg/mL) via subcutaneous injection. Mice Blood samples (0.5 to 1 mL) were taken from the mice before and after the experiments, and after three-week follow-up period, the mice were sacrificed and the spleens were removed for lymphocyte analysis. we found that administration of Herbix at a dose of 300 mg/mL showed the greatest efficacy, characterized by a delay in skin lesion formation, an increment in survival rate and lymphocyte proliferation, upregulation of the gene expression of interferon alpha (IFN-α) and tumor necrosis factor alpha (TNF-α), and an increase in the polarization of cytotoxic and helper T lymphocytes compared to the control group. These results suggest that Herbix at a dose of 300 mg/mL is effective in treating murine herpes and stimulating immune responses, making it a potential candidate for further investigation as an antiherpetic drug.
2016-04-18 | Novel heparan sulfate-binding peptides for blocking herpesvirus entry.
Human cytomegalovirus (HCMV) infection can lead to congenital hearing loss and mental retardation. Upon immune suppression, reactivation of latent HCMV or primary infection increases morbidity in cancer, transplantation, and late stage AIDS patients. Current treatments include nucleoside analogues, which have significant toxicities limiting their usefulness. In this study we screened a panel of synthetic heparin-binding peptides for their ability to prevent CMV infection in vitro. A peptide designated, p5+14 exhibited ~ 90% reduction in murine CMV (MCMV) infection. Because negatively charged, cell-surface heparan sulfate proteoglycans (HSPGs), serve as the attachment receptor during the adsorption phase of the CMV infection cycle, we hypothesized that p5+14 effectively competes for CMV adsorption to the cell surface resulting in the reduction in infection. Positively charged Lys residues were required for peptide binding to cell-surface HSPGs and reducing viral infection. We show that this inhibition was not due to a direct neutralizing effect on the virus itself and that the peptide blocked adsorption of the virus. The peptide also inhibited infection of other herpesviruses: HCMV and herpes simplex virus 1 and 2 in vitro, demonstrating it has broad-spectrum antiviral activity. Therefore, this peptide may offer an adjunct therapy for the treatment of herpes viral infections and other viruses that use HSPGs for entry.
gene therapies
2026-07-24 | Comparative Genomics of Herpes Simplex Virus 2 Isolated from a Maternal-Neonatal Dyad Reveals High Consensus Sequence Homology as Well as Minor Variant Diversity.
Neonatal herpes simplex virus disease most often occurs following mother-to-neonate transmission during childbirth. However, genomic differences between the maternal and neonatal viral populations are poorly understood. Here, we performed deep whole-genome sequencing of clinical HSV-2 samples obtained from a maternal-neonatal dyad to investigate viral population dynamics during transmission.
2026-04-14 | TORCH: Current state of knowledge as of 2025.
The acronym TORCH designates a group of pathogens that can lead to serious pregnancy complications, such as miscarriage, fetal growth restriction, and congenital infections. This review summarizes current insights into these infections, offering practical guidance primarily for obstetricians, infectious disease specialists, and general practitioners involved in prenatal care. The TORCH complex includes Toxoplasma gondii, Rubella virus, Cytomegalovirus (CMV), and Herpes simplex virus (HSV). The definition may be extended to encompass additional (other) pathogens such as Hepatitis B and C viruses (HBV, HCV), Human immunodeficiency virus (HIV), Varicella-zoster virus (VZV), Treponema pallidum (syphilis), Parvovirus B19, and Zika virus. Screening practices for TORCH infections during pregnancy vary significantly across countries. Despite widespread access to medical care and increasing awareness among women planning pregnancy, routine screening for TORCH pathogens is not universally implemented. In Poland, diagnostic procedures during pregnancy are defined by the Standard of Perinatal Care established by the Ministry of Health. This regulation- which replaced earlier recommendations of the Polish Society of Gynecologists and Obstetricians- does not distinguish between ,,mandatory" and ,,recommended" tests but specifies a unified set of investigations to be performed at defined stages of pregnancy. Screening conducted during pregnancy plays a crucial role in detecting previously unrecognized infections. In Poland , a substantial proportion of new diagnoses of HIV, HBV and HCV among young women are made during routine antenatal testing, underscoring the importance of standardized serological screening in prenatal care rather than relying on diagnosis before conception. However, due to their distinct epidemiological and clinical profiles, HIV, HBV, and HCV infections are not discussed in detail in this review.
2021-10-25 | [The role of herpesviruses in development of diseases of the urogenital tract and infertility in women].
This review presents the data on the spreading of all known human herpesviruses (НHVs) in female urogenital tract. According to the WHO almost 500 million people worldwide suffer from genital infection caused by НHVs. НHVs were detected in various inflammatory diseases of female upper and lower genital tract (vaginitis and cervicitis), in extrauterine pregnancy (in fallopian tubes), in infertility (cervical channel, endometrium and ovaries). Herpes simplex virus 1 (HSV‑1) was identified for the first time in oocytes after failed in vitro fertilization (IVF). НHVs produce negative effect on the entire reproductive process from conception to childbirth. It was established that HSV, cytomegalovirus (CMV) and human herpesvirus 6 (HHV-6) markedly increase the risk of spontaneous abortion, preterm birth and stillbirth. Intrauterine НHV infection is a major cause of congenital malformations. Data on humoral and cell immunity in genital herpesvirus infections (НHVI) are also reviewed. Intravaginal HSV‑2 infection changes cell composition of vaginal mucosa, i.e., together with cells mobilized from the blood, protective role is performed by resident memory T‑cells (TRM), natural killer cells (NK‑cells) and regulatory T‑cells (Treg) whose function consists in maintaining the balance of the activities of lymphocytes. Constant НHVI spreading is largely explained by transition of primary infection to potentially reactivating latent form, since latent virus is unavailable to immune recognition and medicines. The genome editing system CRISPR/Cas9 can recognize and modify not only active but also latent viruses. The promising pilot results with the use of this system offer the possibility of developing innovative technologies for НHV elimination and НHVI eradication.
2017-06-02 | CRISPR/Cas9-Mediated Genome Editing of Herpesviruses Limits Productive and Latent Infections.
Herpesviruses infect the majority of the human population and can cause significant morbidity and mortality. Herpes simplex virus (HSV) type 1 causes cold sores and herpes simplex keratitis, whereas HSV-2 is responsible for genital herpes. Human cytomegalovirus (HCMV) is the most common viral cause of congenital defects and is responsible for serious disease in immuno-compromised individuals. Epstein-Barr virus (EBV) is associated with infectious mononucleosis and a broad range of malignancies, including Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's disease, and post-transplant lymphomas. Herpesviruses persist in their host for life by establishing a latent infection that is interrupted by periodic reactivation events during which replication occurs. Current antiviral drug treatments target the clinical manifestations of this productive stage, but they are ineffective at eliminating these viruses from the infected host. Here, we set out to combat both productive and latent herpesvirus infections by exploiting the CRISPR/Cas9 system to target viral genetic elements important for virus fitness. We show effective abrogation of HCMV and HSV-1 replication by targeting gRNAs to essential viral genes. Simultaneous targeting of HSV-1 with multiple gRNAs completely abolished the production of infectious particles from human cells. Using the same approach, EBV can be almost completely cleared from latently infected EBV-transformed human tumor cells. Our studies indicate that the CRISPR/Cas9 system can be effectively targeted to herpesvirus genomes as a potent prophylactic and therapeutic anti-viral strategy that may be used to impair viral replication and clear latent virus infection.
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Drug Discovery Landscape
1 orphan drug designation for Congenital herpes simplex virus infection.
1 orphan drug designation for Congenital herpes simplex virus infection.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
N-Methanocarbathymidine | small molecules | FDA | 2014-10-15 | — | N & N Pharmaceuticals, Inc. |
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