Human Herpes Simplex Virus Type Research Articles

Targeting Peptidylarginine Deiminase 3 to Efficiently Suppress Herpes Simplex Virus Type 2 Infection.

Protein expression is regulated through multiple mechanisms, including post-translational modifications (PTMs), which can alter protein structure, stability, localization, and function. Among these, citrullination stands out due to its ability to convert arginine residues into citrulline, altering protein charge and mass. This modification is catalyzed by calcium-dependent protein arginine deiminases (PADs), enzymes implicated in various inflammatory diseases. We have recently shown that human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1) exploit these enzymes to enhance their replication capabilities. Although the role of PADs in HCMV and HSV-1 infections is well documented, their involvement in HSV-2 infection has not yet been thoroughly investigated. Here, we demonstrate that HSV-2 manipulates the overall protein citrullination profile by activating three PAD isoforms: PAD2, PAD3, and PAD4. However, as previously observed during HSV-1 infection, PAD3 is the most significantly upregulated isoform, both at the mRNA and protein levels. Consistently, we demonstrate that inhibiting PAD3, either through the specific inhibitor CAY10727 or via CRISPR/Cas9-mediated gene silencing, markedly reduces HSV-2 replication and viral protein expression. Lastly, we show that CAY10727 displays an IC50 value of 0.3 μM, which is extremely close to what was previously observed for HSV-1. Overall, our findings highlight the crucial role of PAD3 in the life cycle of HSV-2 and suggest that the targeted inhibition of PAD3 may represent a promising approach for treating HSV-2 infections, especially in cases resistant to existing antiviral therapies.

Herpes Simplex Virus Type 1 Infection of Human Periodontal Ligament.

The periodontal ligament (PDL) is a complex connective tissue that connects the tooth root to the dental alveolar bone and plays crucial mechanical roles. PDL also exhibits regenerative roles and regulatory functions to maintain periodontium integrity and homeostasis. While PDL exposure to oral microbial pathogens is common, virtually nothing is known regarding viral infections of PDL. In particular, human herpes simplex virus type 1 (HSV-1) persistently infects the oral cavity through infections of the oral epithelium, connective tissue and neurons. While the oral spread of HSV-1 is generally asymptomatic, this virus has also been implicated in various oral pathologies. In this study, using a primary cell model derived from PDL (PDL cells), and whole surgical fragments of PDL, we provide evidence supporting the efficient infection of PDL by HSV-1 and the promotion of cytopathic effects. Infection of PDL by HSV-1 was also associated with an acute innate inflammatory response, as illustrated by the production of antiviral interferons and pro-inflammatory cytokines. Furthermore, this inflammatory response to HSV-1 was exacerbated in the presence of bacterial-derived products, such as peptidoglycans. This work therefore highlights the ability of HSV-1 to infect mesenchymal cells from PDL, suggesting that PDL may serve as a viral reservoir for the periodontal spread of HSV-1. Moreover, this raises questions about HSV-1 oral pathogenesis, as HSV-1-associated cytopathic and inflammatory effects may contribute to profound alterations of PDL integrity and functioning.

Antiviral and synergistic effects of photo-energy with acyclovir on herpes simplex virus type 1 infection

This experimental study aimed to evaluate the antiviral and synergistic effects of photoenergy irradiation on human herpes simplex virus type I (HSV-1) infection. We assessed viral replication, plaque formation, and relevant viral gene expression to examine the antiviral and synergistic effects of blue light (BL) with acyclovir treatment. Our results showed that daily BL (10 J/cm2) irradiation inhibited plaque-forming ability and decreased viral copy numbers in HSV-1-infected monkey kidney epithelial Vero cells and primary human oral keratinocyte (HOK) cells. Combined treatment with the antiviral agent acyclovir and BL irradiation increased anti-viral activity, reducing viral titers and copy numbers. In particular, accumulated BL irradiation suppressed characteristic viral genes including UL19 and US6, and viral DNA replication-essential genes including UL9, UL30, UL42, and UL52 in HOK cells. Our results suggest that BL irradiation has anti-viral and synergistic properties, making it a promising therapeutic candidate for suppressing viral infections in clinical trials.

Herpes simplex virus type 1 infection in pet marmoset – case report

A 19-month-old female common marmoset (Callithrix jacchus) was presented with a 4-day history of anorexia and behavioral changes. At presentation, a combination of neurological signs, erosions, and ulcerations of the mucous membranes of the oral mucosa and mucocutaneous junction of the lips were observed, suggesting herpesvirus infection. Although etiological and symptomatic therapy was initiated immediately, the animal died the next day. A necropsy was performed, and gross pathology and pathohistology findings indicated a systemic viral infection. Definitive diagnosis was based on the results of molecular testing that demonstrated the presence of human herpes simplex virus type 1. In conclusion, marmosets are a highly susceptible host for human herpes simplex virus. To reduce the risk of infection and prevent this highly lethal disease in monkeys, contact with humans who have symptomatic or asymptomatic forms of HSV-1 should be limited and accompanied by appropriate hygiene measures.

Pathogen Surveillance for Acute Infectious Conjunctivitis

Acute infectious conjunctivitis is a common ocular condition with major public health consequences. To assess regional variations and microbial etiologies of acute infectious conjunctivitis to guide treatment. In this cross-sectional study, patients with presumed acute infectious conjunctivitis were enrolled in the study at 5 sites (Honolulu, Hawaii; Los Angeles, San Francisco, and San Diego, California; and Petah-Tikva, Israel) from March 2021 to March 2023. Patients with allergic or toxic conjunctivitis were excluded. Pathogens were identified by unbiased RNA deep sequencing. In all, 52 patients (mean [range] age, 48 [7-80] years; 31 females [60%]) were enrolled at 5 sites (6 patients from Honolulu, 9 from San Diego, 11 from Los Angeles, 13 from San Francisco, and 13 from Petah-Tikva). RNA deep sequencing detected human adenovirus species D in one-quarter of patients (13 of 52). A wide range of pathogens, including human coronavirus 229E, SARS-CoV-2, and herpes simplex virus type 1, was also identified, as well as several bacteria and fungi. Moreover, 62% (32 of 52) of patients presented with purulent discharge, while only 8% (4 of 52) of patients had confirmed bacterial pathogens. In this cross-sectional study, pathogens associated with acute infectious conjunctivitis varied between all 5 sites in the US and Israel. Purulent discharge was a common presenting sign in this study, with a low specificity for bacteria-associated conjunctivitis, suggesting that further diagnostic workup may be necessary to inform antibiotic stewardship. Additional research on cost-effectiveness of using RNA deep sequencing is needed to ascertain whether it is better to monitor patients clinically until resolution of disease.

Identification of Na+/K+-ATPase Inhibitor Bufalin as a Novel Pseudorabies Virus Infection Inhibitor In Vitro and In Vivo.

Pseudorabies virus (PRV), an alpha herpesvirus, induces significant economic losses to the swine industry and infects multiple kinds of animals. Therefore, it is of great importance to explore anti-PRV compounds. In this study, to explore the anti-PRV compounds, a library of natural compounds was screened through a cell-based ELISA assay, and it was discovered that bufalin, a Na+/K+-ATPase inhibitor, had a robust inhibitory effect on PRV replication. A time-of-addition experiment and temperature-shift assay showed that bufalin significantly inhibited the entry stage of PRV. NaCl- or KCl-treatment showed that NaCl could enhance the inhibitory effect of bufalin on PRV replication, whereas there was no significant effect under the treatment of KCl. Meanwhile, it was also found that bufalin possessed antiviral activity against other alpha herpesviruses, including human herpes simplex virus type 1 (HSV-1) and chicken Marek's disease virus (MDV). Finally, it was found that bufalin could decrease the viral load in multiple tissues, and reduce the morbidity and mortality in PRV-challenged BALB/c mice. Overall, our findings demonstrated that bufalin has the potential to be developed as an anti-PRV compound.

Secondary Infection Surveillance with Metagenomic Next-Generation Sequencing in COVID-19 Patients: A Cross-Sectional Study.

Metagenomic next-generation sequencing (mNGS) is a promising tool for improving antimicrobial therapy and infection control decision-making in complex infections. Secondary infection surveillance using mNGS in COVID-19 patients has rarely been reported. Respiratory pathogen and antibiotic resistance prediction were evaluated by BALF mNGS for 192 hospitalized COVID-19 patients between December 2022 and February 2023. Secondary infection was confirmed in 83.3% (160/192) of the COVID-19 patients, with bacterial infections (45%, 72/160) predominating, followed by mixed bacterial and fungal infections (20%, 32/160), and fungal infections (17.5%, 28/160). The incidence of bacterial or viral secondary infection was significantly higher in patients who were admitted to the ICU, received mechanical ventilation, or developed severe pneumonia (all p<0.05). Klebsiella pneumoniae (n=30, 8.4%) was the most prevalent pathogen associated with secondary infection followed by Acinetobacter baumannii (n=29, 8.1%), Candida albicans (n=29, 8.1%), Aspergillus fumigatus (n=27, 7.6%), human herpes simplex virus type 1 (n=23, 6.4%), Staphylococcus aureus (n=20, 5.6%) and Pneumocystis jiroveci (n=14, 3.9%). The overall concordance between the resistance genes detected by mNGS and the reported phenotypic resistance in 69 samples containing five clinically important pathogens (ie, K. pneumoniae, A. baumannii, S. aureus, P. aeruginosa and E. coli) that caused secondary infection was 85.5% (59/69). mNGS can detect pathogens causing secondary infection and predict antimicrobial resistance for COVID19 patients. This is crucial for initiating targeted treatment and rapidly detect unsuspected spread of multidrug-resistant pathogens.

Antiviral Potential of Specially Selected Bulgarian Propolis Extracts: In Vitro Activity against Structurally Different Viruses.

Propolis is a natural mixture of resins, wax, and pollen from plant buds and flowers, enriched with enzymes and bee saliva. It also contains various essential oils, vitamins, mineral salts, trace elements, hormones, and ferments. It has been found that propolis possesses antimicrobial, antiviral, and anti-inflammatory properties. We have studied the antiviral activity of six extracts of Bulgarian propolis collected from six districts of Bulgaria. The study was conducted against structurally different viruses: human coronavirus strain OC-43 (HCoV OC-43) and human respiratory syncytial virus type 2 (HRSV-2) (enveloped RNA viruses), human herpes simplex virus type 1 (HSV-1) (enveloped DNA virus), human rhinovirus type 14 (HRV-14) (non-enveloped RNA virus) and human adenovirus type 5 (HadV-5) (non-enveloped DNA virus). The influence of the extracts on the internal replicative cycle of viruses was determined using the cytopathic effect (CPE) inhibition test. The virucidal activity, its impact on the stage of viral adsorption to the host cell, and its protective effect on healthy cells were evaluated using the final dilution method, making them the focal points of interest. The change in viral infectivity under the action of propolis extracts was compared with untreated controls, and Δlgs were determined. Most propolis samples administered during the viral replicative cycle demonstrated the strongest activity against HCoV OC-43 replication. The influence of propolis extracts on the viability of extracellular virions was expressed to a different degree in the various viruses studied, and the effect was significantly stronger in those with an envelope. Almost all extracts significantly inhibited the adsorption step of the herpes virus and, to a less extent, of the coronavirus to the host cell, and some of them applied before viral infection demonstrated a protective effect on healthy cells. Our results enlarge the knowledge about the action of propolis and could open new perspectives for its application in viral infection treatment.

Simian homologues of human herpesviruses and implications for novel viral introduction to free-living mountain gorillas.

The endangered mountain gorilla (Gorilla beringei beringei) in Rwanda, Uganda, and the Democratic Republic of Congo is frequently in contact with humans through tourism, research activities, and illegal entry of people into protected gorilla habitat. Herpesviruses, which are ubiquitous in primates, have the potential to be shared in any setting where humans and gorillas share habitat. Based on serological findings and clinical observations of orofacial ulcerated lesions resembling herpetic lesions, an alpha-herpesvirus resembling human herpes simplex virus type 1 (HSV-1) has long been suspected to be present in human-habituated mountain gorillas in the wild. While the etiology of orofacial lesions in the wild has not been confirmed, HSV-1 has been suspected in captively-housed mountain gorillas and confirmed in a co-housed confiscated Grauer's gorilla (Gorilla beringei graueri). To better characterize herpesviruses infecting mountain gorillas and to determine the presence/absence of HSV-1 in the free-living population, we conducted a population-wide survey to test for the presence of orally shed herpesviruses. DNA was extracted from discarded chewed plants collected from 294 individuals from 26 groups, and samples were screened by polymerase chain reaction using pan-herpesvirus and HSV-1-specific assays. We found no evidence that human herpesviruses had infected free-ranging mountain gorillas. However, we found gorilla-specific homologs to human herpesviruses, including cytomegaloviruses (GbbCMV-1 and 2), a lymphocryptovirus (GbbLCV-1), and a new rhadinovirus (GbbRHV-1) with similar characteristics (i.e., timing of primary infection, shedding in multiple age groups, and potential modes of transmission) to their human counterparts, human cytomegalovirus, Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus, respectively.

High prevalence of sexually transmitted infections among asymptomatic women opting for the intrauterine contraceptive device use in Mwanza, Tanzania: An urgent call for control interventions.

Objective:Placement of intrauterine contraceptive device (IUCD) in asymptomatic woman infected with sexually transmitted infection (STIs) can lead to pelvic inflammatory diseases (PID) and infertility if not well treated. The current study investigated the magnitude of sexually transmitted infections among women opting for IUCD use in the city of Mwanza, Tanzania.Methods:A cross-sectional study involving 150 asymptomatic women was conducted from August to December 2017. Detection of Chlamydia trachomatis antigen from endocervical swabs was done using immunochromatographic rapid tests while sera were used for detection of Treponema pallidum, human immunodeficiency virus (HIV) and herpes simplex virus Type 2 (HSV-2) antibodies.Results:The overall prevalence of STIs was 45/150 (30%, 95% CI: 22–37) while that of individual STIs were 27.3%, 5.3%, and 2.6% for C trachomatis, T pallidum, and HSV-2, respectively. History of dysuria (aOR 6.6; 95% CI 2.3–18.8; p < 0.001) and history of STIs (aOR 4.6; 95%CI 1.0–20.8; p = 0.049) independently predicted presence of STIs.Conclusions:Prevalence of STIs among women opted for IUCD use in the city of Mwanza, Tanzania is alarmingly high and is predicted by past history of dysuria and history of partner’s STIs, calling for the need of screening of the STIs among high-risk women in low- and middle-income countries (LMICs) opting for IUCD use.

Association of bacterial vaginosis with the most common sexually transmitted infections

Introduction/Objective. Bacterial vaginosis (BV) is the most common vaginal dysbiosis that increases the possibility of getting sexually transmitted infections (STI). The objectives of this research are to examine association between BV and the nine most common causes of STIs (Chlamydia trachomatis, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma spp., Trichomonas vaginalis, Neisseria gonorrhoeae, high-risk human papilloma viruses and herpes simplex virus types 1 and 2) and to determine if the presence of BV increases the probability of coinfection with any of the STI microorganisms. Methods. This study involved 235 patients of reproductive age. One sample swab each was collected for vaginal and cervical testing. The vaginal swabs were used for the detection of BV by the reverse transcription polymerase chain reaction (RT-PCR) test. The cervical swabs were used for the detection of the most common STIs, which were tested by four different multiplex RT-PCR tests. Pearson?s ?2 test and Fisher?s probability test were used for statistical analysis of the results. Results. Comparison of the total number of STIs and the condition of the vaginal flora has shown that STIs are the most common in patients with BV (80; 89.9%). Women with BV have a higher frequency of infections with Ureaplasma spp. and M. hominis, 71 (78.9%) and 50 (44.4%), respectively. The presence of detected STI pathogens and relation with the state of vaginal flora indicate that mono infections are present most often in patients with normal flora (51; 42.1%), while coinfections are mostly present in BV patients (50; 55.6%). Conclusion. This study has confirmed the association of M. hominis and Ureaplasma spp. with BV as well as an association of coinfections with this dysbiosis. Better understanding of the association between various STIs and the status of vaginal flora is necessary to enable better diagnosis, prevention of diseases and women?s health protection.

Herpes Simplex Virus and Alzheimer’s Disease: The Present State of Clinical Evidence

Alzheimer´s disease (AD) and dementia have a probably multifactorial pathogenesis and, accordingly to several studies, human herpes simplex virus type 1 (HSV-1) infection may be related. The purpose of this review is to assess the updated clinical evidence towards the association between herpes infection and AD. We performed a PubMed/MEDLINE database research and included in this review randomized clinical trials on the subject of antivirals effectiveness and AD, and observational case-control studies and observational cohort studies regarding AD diagnosis (using clinical and/or histological methods) and HSV-1 detection (using molecular biology or immunohistochemical techniques). A total of 23 case-control and 3 cohort studies met the predetermined inclusion criteria. The results showed that AD was associated with HSV-1 in 22 of the 26 included studies, with most of them confirming that herpes infection is more prevalent in AD patients, when compared to control patients. A possible link between HSV-1 and AD was discussed and many different interpretations and hypothesis were considered. Evidence from observational studies suggests a possible relationship between the two conditions, but the role of HSV-1 infection in the pathogenesis of AD is not completely understood yet. Well-designed and large clinical trials are necessary to endorse this hypothesis and to consider the use of antiviral drugs as a potential alternative for prevention or reduction in the progression rate of AD in the future.

Role of HSV-1 Capsid Vertex-Specific Component (CVSC) and Viral Terminal DNA in Capsid Docking at the Nuclear Pore.

Penetration of the viral genome into a host cell nucleus is critical for initiation of viral replication for most DNA viruses and a few RNA viruses. For herpesviruses, viral DNA ejection into a nucleus occurs when the capsid docks at the nuclear pore complex (NPC) basket with the correct orientation of the unique capsid portal vertex. It has been shown that capsid vertex-specific component (CVSC) proteins, which are located at the twelve vertices of the human herpes simplex virus type 1 (HSV-1) capsid, interact with nucleoporins (Nups) of NPCs. However, it remained unclear whether CVSC proteins determine capsid-to-NPC binding. Furthermore, it has been speculated that terminal DNA adjacent to the portal complex of DNA-filled C-capsids forms a structural motif with the portal cap (which retains DNA in the capsid), which mediates capsid-NPC binding. We demonstrate that terminal viral DNA adjacent to the portal proteins does not present a structural element required for capsid-NPC binding. Our data also show that level of CVSC proteins on the HSV-1 capsid affects level of NPC binding. To elucidate the capsid-binding process, we use an isolated, reconstituted cell nucleus system that recapitulates capsid-nucleus binding in vivo without interference from trafficking kinetics of capsids moving toward the nucleus. This allows binding of non-infectious capsid maturation intermediates with varying levels of vertex-specific components. This experimental system provides a platform for investigating virus–host interaction at the nuclear membrane.

The Analysis of Herpes Simplex Virus Type 1 (HSV-1)-Encoded MicroRNAs Targets: A Likely Relationship of Alzheimer's Disease and HSV-1 Infection.

Alzheimer's disease (AD), the most frequently diagnosed dementia, is a senile neurodegenerative disorder characterized by amnesia and cognitive dysfunction. Unfortunately, there are still no successful strategies to prevent AD progression. Thus, the vast majority of research focuses on recognizing risk factors for developing and progressing this disease. Human spirochetes, fungi, Borrelia burgdorferi, Chlamydophila pneumoniae, Helicobacter pylori, and human herpes simplex virus type 1 (HSV-1) have all been implicated in the development and progression of AD. Identifying microRNAs (miRs) encoded by DNA viruses has indicated that viruses can be evolved to exploit RNA silencing to regulate host and viral genes. Similar to host miR, v-miR can interact with the 3' untranslated region (UTR) of the target mRNA to regulate gene expression. Although HSV-1 can also encode various miRs, their significance in the development and progression of AD is still unclear. In the present study, utilizing the bioinformatics approach (R software and related packages), we analyzed the differentially expressed genes (DEGs) in AD samples (grey matter) of GSE37263 dataset obtained from the NCBI Gene Expression Omnibus (GEO). Then, the sequences of HSV-1-encoded-miRs were retrieved from miRbase, and their targets were predicted by miRDB. Afterward, the common genes between downregulated DEGs in AD and targets of HSV-1-encoded miRs were identified to shed new light on the relationship between HSV-1 infection and AD development. Our results have indicated that HSV-1-encoded-miRs can target the downregulated DEGs in AD, and these aberrant interactions can offer valuable diagnostic/prognostic biomarkers for affected patients.

Rational Design of Live-Attenuated Vaccines against Herpes Simplex Viruses.

Diseases caused by human herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) affect millions of people worldwide and range from fatal encephalitis in neonates and herpes keratitis to orofacial and genital herpes, among other manifestations. The viruses can be shed efficiently by asymptomatic carriers, causing increased rates of infection. Viral transmission occurs through direct contact of mucosal surfaces followed by initial replication of the incoming virus in skin tissues. Subsequently, the viruses infect sensory neurons in the trigeminal and lumbosacral dorsal root ganglia, where they are primarily maintained in a transcriptionally repressed state termed “latency”, which persists for the lifetime of the host. HSV DNA has also been detected in other sympathetic ganglia. Periodically, latent viruses can reactivate, causing ulcerative and often painful lesions primarily at the site of primary infection and proximal sites. In the United States, recurrent genital herpes alone accounts for more than a billion dollars in direct medical costs per year, while there are much higher costs associated with the socio-economic aspects of diseased patients, such as loss of productivity due to mental anguish. Currently, there are no effective FDA-approved vaccines for either prophylactic or therapeutic treatment of human herpes simplex infections, while several recent clinical trials have failed to achieve their endpoint goals. Historically, live-attenuated vaccines have successfully combated viral diseases, including polio, influenza, measles, and smallpox. Vaccines aimed to protect against the devastation of smallpox led to the most significant achievement in medical history: the eradication of human disease by vaccination. Recently, novel approaches toward developing safe and effective live-attenuated vaccines have demonstrated high efficacy in various preclinical models of herpetic disease. This next generation of live-attenuated vaccines has been tailored to minimize vaccine-associated side effects and promote effective and long-lasting immune responses. The ultimate goal is to prevent or reduce primary infections (prophylactic vaccines) or reduce the frequency and severity of disease associated with reactivation events (therapeutic vaccines). These vaccines’ “rational” design is based on our current understanding of the immunopathogenesis of herpesviral infections that guide the development of vaccines that generate robust and protective immune responses. This review covers recent advances in the development of herpes simplex vaccines and the current state of ongoing clinical trials in pursuit of an effective vaccine against herpes simplex virus infections and associated diseases.

Analysis of optimal control strategy on transmission dynamics of HPV-HSV-II coinfection model

In this paper, optimal control problem is applied to Human Papillomavirus (HPV) and Herpes simplex virus type 2 (HSV-2) coinfection model formulated by a system of ordinary differential equations. Optimal control strategy is employed to study the effect of combining different intervention strategy on the transmission dynamics of HPV-HSV-II coinfection diseases. The necessary conditions for the existence of the optimal controls are established using Pontryagin’s Maximum Principle. Optimal control systems were performed with help of Runge-Kutta forward-backward sweep numerical approximation method. Finally, numerical simulation illustrated that a combination of all controls is the most effective strategy to minimize the disease from the community. The results shows that the size of infectious population are minimized by using different control strategies.

Molecular genetic and clinical aspects of socially relevant viruses underlying congenital diseases

Congenital viral infectious diseases are characterized by polyetiologic pathology holding an important place in the structure of perinatal losses. Due to the wide distribution and lack of specific prophylaxis, the problem of herpesvirus infections is of greatest interest, namely of herpes infection caused by herpes simplex virus type 1 and 2, human herpes simplex virus type 6 and cytomegalovirus infection, as well as parvovirus infection B19. The opportunities to investigate a relation between manifestations of the infectious process and host molecular genetic characteristics have been expanded after developing full genome sequencing methods and creating genetic data international banks. It has been proven that herpes virus genetic variations can account for related neurovirulence, showing that diverse cytomegalovirus genotypes are associated with hepatosplenomegaly, hearing impairment and the symptoms of the central nervous system diseases. Nevertheless, the data on correlation between genotypes and clinical manifestations are still scarce and contradictory, whereas high level of variability becomes extremely evident while comparing genomic sequences of viral strains. The herpesvirus type 6 has been proven to integrate into germ cells with potential for subsequent vertical transmission of chromosomally integrated virus to the offspring and its further intergeneration inheritance. А direct relationship between B19V genospecies and disease manifestations including congenital infections has not yet been identified. Taking into account possible differences in the geographical distribution of such viruses on the territory of the Russian Federation, ethnic populational characteristics, and high frequency of related congenital infectious diseases with a wide range of clinical manifestations, it seems promising to expand scientific research on the genotyping of herpes simplex viruses, cytomegalovirus, herpes viruses type 6 and parvovirus B19V in Russia. The results of such studies will be demanded by practical healthcare in order to develop and use more effective etiotropic drugs and specific prophylaxis in the light of trends to develop personalized and preventive medicine.

Comparative Analysis of Serological Markers of Herpes Viruses and Hypergammaglobulinaemia in Patients with Angioimmunoblastic T-Cell Lymphoma

Introduction: Angioimmunoblastic T-cell lymphoma (AITL) is a peripheral T-cell lymphoma characterized by generalized lymphadenopathy, hepatosplenomegaly and dysproteinemia. Some believe that AITL is associated with herpes viruses, especially Epstein-Barr virus (EBV). It has been speculated that herpes viruses can directly or indirectly trigger this disorder and induce abnormal hyperimmune reaction, manifested by hypergammaglobulinaemia in 50-83% pts. So antiviral antibodies, mainly anti-EBV, are suggested as hypergammaglobulinaemia substrate.Aim: The aim of the study was to compare serological markers of herpes viruses and gammapathy presence in patients at the onset of AITL.Patients and methods: 25 patients with AITL were enrolled in the study, the male/female ratio was 16/9; median age was 63 (29-81) years. Diagnosis AITL was based on standard WHO criteria. Antiviral antibodies against human cytomegalovirus (HCMV), Epstein-Barr virus (EBV) and Herpes simplex virus types 1 and 2 (HSV 1, 2) were investigated: IgM and IgG titers were tested in ELISA. Titer of anti-HCMV-IgG and anti-HSV 1, 2 IgG corresponding to a dilution of 1:3200 and further was considered as high. Concentration of anti-EBNA-1-IgG 60 c.u. (conventional units) and more was considered as high. Immunochemical studies of blood serum included serum protein electrophoresis/immunofixation, nephelometric quantification of total immunoglobulins, serum free light chain assay.Results: Polyclonal hypergammaglobulinaemia was revealed in 14 (56%) of 25 pts: 10 cases of polyclonal IgG and 10 cases of polyclonal IgM hypergammaglobulinaemia (6 pts had IgM and IgG hypergammaglobulinaemia simultaneously). Hypogammaglobulinaemia was detected in 8 (15%) of 25 cases: decreased level of IgG was observed in 8 pts, IgM - in 4 pts. Serological markers of active herpes virus infections (antiviral IgM) were found in 13 (52%) of 25 pts: anti-EBV-IgM was detected only in 3 (12%) cases, anti-HSV 1, 2 IgM - in 10 (40%) of 25 cases and anti-HCMV-IgM - in 4 (16%) cases. Two patients had antiviral IgM against 2 viruses and 1 patient against 3 viruses simultaneously. So the anti-HSV 1,2 IgM not anti-EBV-IgM demonstrated the highest detection rate unexpectedly. Increased level of antiviral IgG was determined in 21 (84%) of 25 pts. Increased concentration (65 and more c.u.) of anti-EBNA-1-IgG was revealed in 16 (64%) cases, elevated titer of anti-HSV 1, 2 IgG - in 19 (76%) of 25 pts, excessed level of anti-HCMV IgG was observed in 6 pts. Thus, HSV 1,2 turned out to be the most frequent cause of antiviral IgG increased level.A comparison of immunochemical and virological data was carried out. Antiviral IgM was detected in 10 out of 10 cases with polyclonal IgM hypergammaglobulinaemia (9 were anti-HSV 1,2-IgM positive). The rest 3 antiviral IgM positive patients showed no signs of polyclonal IgM exceeding the reference values (Table 1). There wasn't a case of polyclonal IgM hypergammaglobulinaemia without antiviral IgM, what are points out to a strong correlation (p=0.021).Elevated level of antiviral IgG was detected in 8 out of 10 (80%) cases of polyclonal IgG hypergammaglobulinaemia (Table 2). Two cases of polyclonal IgG hypergammaglobulinaemia were not accompanied by an increased level of antiviral IgG, and on the contrary 7 out of 8 (75%) cases of hypogammaglobulinaemia were accompanied by an excess of antiviral IgG (mostly due to EBV and HSV 1, 2). Thus, there was no correlation between polyclonal IgG hypergammaglobulinaemia and antiviral IgG elevation (0.366<p<0.975).Conclusion: No evidence of contribution of herpes virus-induced humoral responce to polyclonal hypergammaglobulinaemia class G was observed (0.366<p<0.975). In cases with polyclonal hypergammaglobulinaemia class M, on the contrary, the connection could be suspected. It seems that HSV 1, 2 induces the maximum contribution to the hypergammaglobulinaemia class M [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Discovery of Novel Herpes Simplexviruses in Wild Gorillas, Bonobos, and Chimpanzees Supports Zoonotic Origin of HSV-2

Viruses closely related to human pathogens can reveal the origins of human infectious diseases. Human herpes simplexvirus type 1 (HSV-1) and type 2 (HSV-2) are hypothesized to have arisen via host-virus codivergence and cross-species transmission. We report the discovery of novel herpes simplexviruses during a large-scale screening of fecal samples from wild gorillas, bonobos, and chimpanzees. Phylogenetic analysis indicates that, contrary to expectation, simplexviruses from these African apes are all more closely related to HSV-2 than to HSV-1. Molecular clock-based hypothesis testing suggests the divergence between HSV-1 and the African great ape simplexviruses likely represents a codivergence event between humans and gorillas. The simplexviruses infecting African great apes subsequently experienced multiple cross-species transmission events over the past 3 My, the most recent of which occurred between humans and bonobos around 1 Ma. These findings revise our understanding of the origins of human herpes simplexviruses and suggest that HSV-2 is one of the earliest zoonotic pathogens.

Herpes Simplex Virus and Alzheimer’s Disease: The Present State of Clinical Evidence

Alzheimer´s disease (AD) and dementia have a probably multifactorial pathogenesis and, accordingly to several studies, human herpes simplex virus type 1 (HSV-1) infection may be related. The purpose of this review is to assess the updated clinical evidence towards the association between herpes infection and AD. We performed a PubMed/MEDLINE database research and included in this review randomized clinical trials on the subject of antivirals effectiveness and AD, and observational case-control studies and observational cohort studies regarding AD diagnosis (using clinical and/or histological methods) and HSV-1 detection (using molecular biology or immunohistochemical techniques). A total of 23 case-control and 3 cohort studies met the predetermined inclusion criteria. The results showed that AD was associated with HSV-1 in 22 of the 26 included studies, with most of them confirming that herpes infection is more prevalent in AD patients, when compared to control patients. A possible link between HSV-1 and AD was discussed and many different interpretations and hypothesis were considered. Evidence from observational studies suggests a possible relationship between the two conditions, but the role of HSV-1 infection in the pathogenesis of AD is not completely understood yet. Well-designed and large clinical trials are necessary to endorse this hypothesis and to consider the use of antiviral drugs as a potential alternative for prevention or reduction in the progression rate of AD in the future.