Human Herpes Virus Type 2 ( HSV2 ), Human Cytomegalovirus (HCMV) in the Male Genital Tract and Fertilization

The possibility of infection of the human male genital tract by human herpes virus type 2 (HSV2) or human cytomegalovirus (HCMV) is well established and their sexual transmission has been the object of many studies. Moreover, medically assisted procreation, which helps in numerous fertility problems, raises the question of new viral risks linked to the application of these new technologies. In this review, we shall consider current knowledge in terms of the presence of HSV 2 and HCMV in the different parts of the genital tract of immunocompetent or immunodepressed men. We shall also consider the possibility of viral transmission by the sexual act or by the various techniques used in medically assisted procreation. We shall describe studies in human beings and in animals.

Advances in Detection Methods of Koi Herpes Virus

Koi herpes virus is a new virus found in the aquaculture production of Cryprinus carpiod and common carp in recent years. Currently, virus isolation and identification is still the traditional method for the detection of Koi herpes virus, while molecular biology detection method has become the current developmental di- rection due to its characteristics of more sensitive, specific and rapid. Furthermore, people are still committed to exploring new detection methods for the detection of Koi herpes vires. In this paper, traditional and newly-developed detection methods of Koi herpes vires in recent years were summarized, in order to provide refer- ence for further exploring rapid and accurate diagnostic detection method.

Establishment and Application of the TaqMan Real-Time Fluorescence Quantitative PCR Detection Assay for Koi Herpes Virus

[ Objective ] This study aimed to establish a rapid and effective quarantine method of Koi herpes virus. [ Method] Primers and corresponding TaqMan probe were designed based on the conserved sequence of Koi herpes virus （KHV） pol-ymerase gene （Sph） to establish a rapid and effective fluorescence quantitative PCR method for Koi herpes virus detection. The cell cultures were detected by using the established fluorescence quantitative PCR assay, and the results were com- pared with that of conventional PCR. [ Result] The sensitivity of fluorescence quantitative PCR was higher than that of conventional PCR. The minimum copy num- ber that could be detected was 1.6 - 102 copies/p.1. The established method was adopted for sample detection, and a reliable diagnostic result could be obtained within 4 h. [Conclusion] The established method is rapid, sensitive, specific and repeatable, which is conducive to the rapid detection of Koi herpes virus. Key words Koi herpes virus; Fluorescence quantitative PCR; Detection

Evaluation of the effects of acyclovir and/or human amniotic membrane on herpes virus culture and quantitative virus inactivity by real-time polymerase chain reaction

·AIM: To investigate the permeability of amniotic membrane in herpes virus cell culture to acyclovir with real time polymerase chain reaction(RT-PCR).·METHODS: Madin-Darby Bovine Kidney(MDBK) cell culture and Bovine Herpes Virus(BHV1) type 1 were used in the study. Cell cultures were grouped into two on the basis of herpes virus inoculation. Each group was sub-grouped into three. Amniotic membrane(V-HAM),acyclovir(V-A), and amniotic membrane and acyclovir(V-HAM-A) were applied to these subgroup cultures,respectively. After the application of the membrane and the drug, the cultures were evaluated at 24 and 48 h for cytopathic effect positive(CPE +) with a tissue culture microscope. In the CPE(+) samples, the DNA was extracted for viral DNA analysis by RT-PCR.·RESULTS: In control cultures without herpes virus CPE was not detected. Besides, amniotic membrane and acyclovir did not have cytotoxic effect on cell cultures.CPE were detected in Bovine Herpesvirus type-1inoculated cell cultures after amniotic membrane and/or acyclovir application. DNA analysis with RT-PCR indicated that Cycle threshold(Ct) values were lower in the BHV1 and membrane applied group(amniotic membrane group 【 acyclovir group 【 membrane and acyclovir group). This showed that membrane did not have antiviral effect. The membrane and acyclovir cell culture groups with high Ct values indicated thatmembrane was permeable and had a low barrier effect to drug.·CONCLUSION: In our in-vitro study, we found that amniotic membrane, which can be used in the treatment of corneal diseases, did not have antiviral effect. Besides,we detected that amniotic membrane was permeable to acyclovir in BHV-1 inoculated MDBK cell culture.However, more studies are necessary to investigate the quantitative effects of amniotic membrane and acyclovir.

Interleukin 1βreceptor and synaptic dysfunction in recurrent brain infection with Herpes simplex virus type-1

Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.

Herpes Simplex Virus Encephalitis Complicated by Acute Ischemic Stroke

Introduction: Herpes simplex virus is the most common etiology for life-threatening sporadic encephalitis worldwide. Antiviral therapy with acyclovir has been shown to reduce mortality and should be started promptly in patients with clinically suspected viral encephalitis before serological confirmation of the diagnosis. Despite antiviral treatment, it is associated with significant mortality and a wide range of neurologic sequelae or neuropsychiatric disorders. Clinical presentation includes fever, headache, altered mental status, and focal or generalized seizures. In some cases, it can present with focal neurological deficits, such as an acute stroke. The aim of this study is to identify rare complications of HSVE. Presentation: We present a case of a 71-year-old female patient with herpes virus encephalitis and an ischemic cerebral accident. The findings of CT scan of the brain revealed an extensive right temporal hypodensity. CSF findings include an elevated protein level, normal glucose level and pleocytosis with lymphocyte predominance. The lumbar tap confirmed the presence of herpes simplex virus type 1 with polymerase chain reaction (PCR) in the CSF. Neurological manifestations include focal neurological deficit with left-sided hemiparesis and coma. After 40 days of complex therapy, an improvement in the mental state was observed. Conclusion: There are varying degrees of neurologic sequelae among survivors in children and adults despite the antiviral treatment. Herpes simplex encephalitis has significant morbidity and high mortality due to the lack of prophylactic treatment and preventable strategies.

Role of viruses in periodontitis:An extensive review of herpesviruses,human immunodeficiency virus,coronavirus-19,papillomavirus and hepatitis viruses

Periodontitis is the inflammation of the supporting structures around the dentition.Several microbial agents,mostly bacteria,have been identified as causative factors for periodontal disease.On the other hand,oral cavity is a rich reservoir for viruses since it contains a wide variety of cell types that can be targeted by viruses.Traditionally,the focus of research about the oral flora has been on bacteria because the most widespread oral diseases,like periodontitis and dental caries,are outcomes of bacterial infection.However,recently and especially after the emergence of coronavirus disease 2019,there is a growing tendency toward including viruses also into the scope of oral microbiome investigations.The global high prevalence of periodontitis and viral infections may point out to a concomitant or synergistic effect between the two.Although the exact nature of the mechanism still is not clearly understood,this could be speculated through the manipulation of the immune system by viruses;hence facilitating the furthermore colonization of the oral tissues by bacteria.This review provides an extensive and detailed update on the role of the most common viruses including herpes family(herpes simplex,varicella-zoster,Epstein-Barr,cytomegalovirus),Human papillomaviruses,Human immunodeficiency virus and severe acute respiratory syndrome coronavirus 2 in the initiation,progression and prognosis of periodontitis.

Regional prevalence and transmission route of Kaposi＇s sarcoma-associated herpes virus in Zhejiang, China

Background The infection of Kaposi＇s sarcoma-associated herpes virus （KSHV） is most likely the cause of clinical Kaposi＇s sarcoma,primary effusion lymphoma,and multi-center Castleman＇s disease.KSHV infection has very limited epidemiological survey data in China,and its definite mode of transmission remains controversial.This study aimed to determine the infection status and the main transmission route of KSHV in Chinese population.Methods An enzyme-linked immunosorbent assay （ELISA） utilizing KSHV ORF65 recombinant protein was employed to analyze the antibody response to KSHV ORF65 in sera from 122 healthy physical examination people,107intravenous drug users,135 non-intravenous drug users,211 hepatitis B （HBV） patients infected via blood transmission,107 kidney transplant recipients,and 72 female sex workers in Zhejiang Province in Southeast China.Results KSHV infection occurred relatively common （13.1%） in healthy population in Zhejiang,China.Infection rate was 16.7% in female sex workers,but significantly elevated in intravenous drug addicts （58.9%）,blood-transmitted HBV patients （28.0%） and kidney transplant patients （41.1%）.Conclusion Blood borne transmission of KSHV is probably the main route of infection in Zhejiang Province.

Oxidative stress favours herpes virus infection in vertebrates： a meta-analysis

Herpes viruses are responsible for a variety of pathological effects in humans and in both wild and domestic animals. One mechanism that has been proposed to facilitate replication and activity of herpes viruses is oxidative stress （OS）. We used meta-analytical techniques to test the hypotheses that （1） herpes virus infection causes OS and （2） supplementation of antioxidants reduces virus load, indicating that replication is favoured by a state of OS. Results based on studies on mammals, including humans, and birds show that （1） OS is indeed increased by herpes virus infection across multiple tissues and species, （2） biomarkers of OS may change differently between tissues, and （3） the effect size does not differ among different virus strains. In addition, the increase of oxidative damage in blood （tissue commonly available in ecological studies） was similar to that in the tissues most sensitive to the herpes virus. Our results also show that administration of antioxidants re- duces virus yield, indicating that a condition of OS is favorable for the viral replication. In addition, some antioxidants may be more efficient than others in reducing herpes virus yield. Our results point to a potential mechanism linking herpes virus infection to individual health status.

New strategies against drug resistance to herpes simplex virus

Herpes simplex virus （HSV）, a member of the Herpesviridae family, is a significant human pathogen that results in mucocutaneous lesions in the oral cavity or genital infections. Acyclovir （ACV） and related nucleoside analogues can successfully treat HSV infections, but the emergence of drug resistance to ACV has created a barrier for the treatment of HSV infections, especially in immunocompromised patients. There is an urgent need to explore new and effective tactics to circumvent drug resistance to HSV. This review summarises the current strategies in the development of new targets （the DNA helicase/primase （H/P） complex）, new types of molecules （nature products） and new antiviral mechanisms （lethal mutagenesis of Janus-type nucleosides） to fight the drug resistance of HSV.

In vitro Anti-viral Activity of the Total Alkaloids from Tripterygium hypoglaucum against Herpes Simplex Virus Type 1

Herpes simplex virus type 1 （HSV-1） is a commonly occurring human pathogen worldwide. There is an urgent need to discover and develop new alternative agents for the management of HSV-1 infection. Tripterygium hypoglaucum （level） Hutch （Celastraceae） is a traditional Chinese medicine plant with many pharmacological activities such as anti-inflammation, anti-tumor and antifertility. The usual medicinal part is the roots which contain about a 1% yield of alkaloids. A crude total alkaloids extract was prepared from the roots of T. hypoglaucum amd its antiviral activity against HSV-1 in Vero cells was evaluated by cytopathic effect （CPE） assay, plaque reduction assay and by RT-PCR analysis. The alkaloids extract presented low cytotoxicity （CC50 = 46.6μg/mL） and potent CPE inhibition activity, the 50% inhibitory concentration （ICs0） was 6.5 μg/mL, noticeably lower than that of Acyclovir （15.4μg /mL）. Plaque formation was significantly reduced by the alkaloids extract at concentrations of 6.25 μg/mL to 12.5 μg/mL, the plaque reduction ratio reached 55% to 75% which was 35% higher than that of Acyclovir at the same concentration. RT-PCR analysis showed that, the transcription of two important delayed early genes UL30 and UL39, and a late gene US6 of HSV-1 genome all were suppressed by the alkaloids extract, the expression inhibiting efficacy compared to the control was 74.6% （UL30）, 70.9% （UL39） and 62.6% （US6） respectively at the working concentration of 12.5μg/mL. The above results suggest a potent anti-HSV-1 activity of the alkaloids extract in vitro.

The Herpes Simplex Virus Type 1 Multiple Function Protein ICP27

The herpes simplex virus type 1 （HSV-1） infected-cell protein 27 （ICP27） is an essential, highly conserved protein involved in various steps of HSV-1 gene regulation as well as in the shut-off of host gene expression during infection. It functions primarily at the post-transcriptional level in inhibiting precursor mRNA splicing and in promoting nuclear export of viral transcripts. Recently, many novel functions performed by the HSV- 1 ICP27 protein were shown, including leptomycin B resistance, inhibition of the type I interferon signaling, regulation of the viral mRNA translation and determining the composition of HSV-1 virions

Asymptomatic seminal infection of herpes simplex virus:impact on male infertility

In more than half of infertile men, the cause of their infertility is unknown. Several studies revealed the role of viral infections in male infertility. The aim of the present study was to determine the prevalence of herpes simplex virus-1 （HSV-1） and HSV-2 in semen from asymptomatic infertile male patients, and its association with altered semen parameters. A total of 70 semen samples were collected from infertile men who attended the Research and Clinical Center for Infertility in Yazd, Iran. Semen analysis and diagnostic real-time PCR using specific primers and probes for HSV-1 and HSV-2 DNA were performed. Comparison of semen parameters between virally in- fected and non-infected samples were performed with independent t-test and Mann-Whitney test. Semen analysis showed that infertile men fell into two groups, the male factor group and the unexplained group. HSV-1 and HSV-2 DNA was detected in 16 （22.9%） and 10 （14.3%） of 70 semen samples, respectively. All HSV-positive samples had abnormal semen parameters （the male factor group）. Although HSV infection was not associated with sperm motility and morphological defects, it was correlated with lower sperm count in the seminal fluid. The findings suggest that asymptomatic seminal infection of HSV plays an important role in male infertility by adversely af- fecting sperm count.

The miRNAs of Herpes Simplex Virus(HSV)

Herpes simplex virus (HSV) is a group of common human pathogens with two serotypes HSV-1 and HSV-2.The prevalence of HSV is worldwide.It primarily infects humans through epithelial cells,when it introduces a latent infection into the nervous system.During viral latency,only a region known as the latency-associated transcript (LAT) is expressed.The discovery of HSV miRNAs helps to draw a larger picture of the infection and pathogenesis of the virus.This review summarizes miRNAs found in HSV-1 and HSV-2 so far.The functional studies of miRNAs in HSV to date indicate that they play a stage-specific role coordinated with viral proteins to maintain the virus life cycle.

Feasibility of herpes simplex virus type 1 mutants labeled with radionuclides for tumor treatment

For over one hundred years, viruses have been recognized as capable of killing tumor cells. At present, people are still researching and constructing more suitable oncolytic viruses for treating different malignant tumors. Although extensive studies have demonstrated that herpes simplex virus type 1 (HSV-1) is the most potential oncolytic virus, therapies based on herpes simplex virus type 1 vectors still arouse bio-safety and risk management issues. Researchers have therefore introduced the new idea of treating cancer with HSV-1 mutants labeled with radionuclides, combining radionuclide and oncolytic virus therapies. This overview briefly summarizes the status and mechanisms by which oncolytic viruses kill tumor cells, discusses the application of HSV-1 and HSV-1 derived vectors for tumor therapy, and demonstrates the feasibility and prospect of HSV-1 mutants labeled with radionuclides for treating tumors.

The Importance of Heparan Sulfate in Herpesvirus Infection

Herpes simplex virus type-1 (HSV-1) is one of many pathogens that use the cell surface glycosaminoglycan heparan sulfate as a receptor. Heparan sulfate is highly expressed on the surface and extracellular matrix of virtually all cell types making it an ideal receptor. Heparan sulfate interacts with HSV-1 envelope glycoproteins gB and gC during the initial attachment step during HSV-1 entry. In addition,a modified form of heparan sulfate,known as 3-O-sulfated heparan sulfate,interacts with HSV-1 gD to induce fusion between the viral envelope and host cell membrane. The 3-O-sulfation of heparan sulfate is a rare modification which occurs during the biosynthesis of heparan sulfate that is carried out by a family of enzymes known as 3-O-sulfotransferases. Due to its involvement in multiple steps of the infection process,heparan sulfate has been a prime target for the development of agents to inhibit HSV entry. Understanding how heparan sulfate functions during HSV-1 infection may not only be critical for inhibiting infection by this virus,but it may also be crucial in the fight against many other pathogens as well.

Contributions of neurotropic human herpesviruses herpes simplex virus 1 and human herpesvirus 6 to neurodegenerative disease pathology

Human herpesviruses （HVs） have developed ingenious mechanisms that enable them to traverse the defenses of the central nervous system （CNS）. The ability of HVs to enter a state of latency, a defining char- acteristic of this viral family, allows them to persist in the human host indefinitely. As such, HVs represent the most frequently detected pathogens in the brain. Under constant immune pressure, these infections are largely asymptomatic in healthy hosts. However, many neurotropic HVs have been directly connected with CNS pathology in the context of other stressors and genetic risk factors. In this review, we discuss the potential mechanisms by which neurotropic HVs contribute to neurodegenerative disease （NDD） patholo- gy by highlighting two prominent members of the HV family, herpes simplex virus 1 （HSV-1） and human herpesvirus 6 （HHV-6）. We （i） introduce the infectious pathways and replicative cycles of HSV-1 and HHV-6 and then （ii） review the clinical evidence supporting associations between these viruses and the NDDs Alzheimer＇s disease （AD） and multiple sclerosis （MS）, respectively. We then （iii） highlight and dis- cuss potential mechanisms by which these viruses exert negative effects on neurons and glia. Finally, we （iv） discuss how these viruses could interact with other disease-modifying factors to contribute to the initiation and/or progression of NDDs.

A functional type I interferon pathway drives resistance to cornea herpes simplex virus type 1 infection by recruitment of leukocytes

Type I interferons are critical antiviral cytokines produced following herpes simplex virus type-1 （HSV-1） infection that act to inhibit viral spread. In the present study, we identify HSV-infected and adjacent uninfected corneal epithelial cells as the source of interferon-a. We also report mice deficient in the A1 chain of the type I IFN receptor （CDl18-/） are extremely sensitive to ocular infection with low doses （100 PFU） of HSV-1 as seen by significantly elevated viral titers in the cornea Compared to wild type （WT） controls. The enhanced susceptibil- ity correlated with a loss of CD4＋ and CD8＋ T cell recruitment and aberrant chemokine production in the cornea despite mounting an adaptive immune response in the draining mandibular lymph node of CDll8/ mice. Taken together, these results highlight the importance of IFN production in both the innate immune response as well as eliciting chemokine production required to facilitate adaptive immune cell trafficking.

The Herpes Simplex Virus Type 1 Infected Cell Protein 22

As one of the immediate-early(IE)proteins of herpes simplex virus type 1(HSV-1),ICP22 is a multifunctional viral regulator that localizes in the nucleus of infected cells.It is required in experimental animal systems and some nonhuman cell lines,but not in Vero or HEp-2 cells.ICP22 is extensively phosphorylated by viral and cellular kinases and nucleotidylylated by casein kinase Ⅱ.It has been shown to be required for efficient expression of early(E)genes and a subset of late(L)genes.ICP22,in conjunction with the UL13 kinase,mediates the phosphorylation of RNA polymerase Ⅱ.Both ICP22 and UL13 are required for the activation of cdc2,the degradation of cyclins A and B and the acquisition of a new cdc2 partner,the UL42 DNA polymerase processivity factor.The cdc2-UL42 complex mediates postranscriptional modification of topoisomerase Ⅱα in an ICP22-dependent manner to promote L gene expression.In addition,ICP22 interacts with cdk9 in a Us3 kinase dependent fashion to phosphorylate RNA polymerase Ⅱ.

Current Status of Natural Products from Plants as Anti-herpes Simplex Virus 1 Agents

Nucleoside analogues have been the mainstay of clinical treatment of herpes simplex virus 1 (HSV-1) infections since their development. However, the emergence of drug resistant strains has underlined the urgency of the discovery of novel anti-HSV-1 drugs. Natural products, which provided many novel drug leads, are known to be an important source of anti-HSV-1 agents. Herein, we present an overview of natural products with anti-HSV-1 activities isolated from a variety of plants reported in recent years. Several different compounds, mainly belonging to the three groups of polysaccharides, polyphenols and terpenes, showed antiviral effects against HSV-1, indicating their potential to be promising anti-HSV-1 agents.