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serologic screening for genital herpes: an updated evidence report and systematic review for the us preventive services task force.genital herpes simplex virus (hsv) infection is a prevalent sexually transmitted infection. vertical transmission of hsv can lead to fetal morbidity and mortality.201627997660
effect of pritelivir compared with valacyclovir on genital hsv-2 shedding in patients with frequent recurrences: a randomized clinical trial.current therapy of herpes infections relies on nucleoside analogues. pritelivir is a well-tolerated novel herpes simplex virus (hsv) helicase-primase inhibitor that reduced genital shedding and lesions.201627997653
hla class i and ii alleles, heterozygosity and hla-kir interactions are associated with rates of genital hsv shedding and lesions.variation at hla and kir loci is associated with the severity of viral infections. to assess associations of genital hsv-2 infection with human hla and kir genetic loci, we measured the frequencies of genital herpes simplex virus (hsv) dna detection and of genital lesions in hsv-2 seropositive persons. we followed 267 hsv-2 seropositive persons who collected daily genital swabs and recorded lesions for ⩾30 days. all persons were laboratory-documented as hiv-seronegative, and all were caucasian b ...201627853144
intravaginal practices and prevalence of sexual and reproductive tract infections among women in rural malawi.many women engage in intravaginal practices (ivp) with a goal of improving genital hygiene and increasing sexual pleasure. intravaginal practices can disrupt the genital mucosa, and some studies have found that ivp increases risk of acquisition of hiv and bacterial vaginosis (bv). limited prior research also suggests significant associations between ivp, herpes simplex virus type 2 (hsv-2), and high-risk types of human papillomavirus (hpv).201627835627
herpes simplex virus suppressive therapy in herpes simplex virus-2/human immunodeficiency virus-1 coinfected women is associated with reduced systemic cxcl10 but not genital cytokines.herpes simplex virus type-2 (hsv-2) may heighten immune activation and increase human immunodeficiency virus 1 (hiv-1) replication, resulting in greater infectivity and faster hiv-1 disease progression. an 18-week randomized, placebo-controlled crossover trial of 500 mg valacyclovir twice daily in 20 antiretroviral-naive women coinfected with hsv-2 and hiv-1 was conducted and hsv-2 suppression was found to significantly reduce both hsv-2 and hiv-1 viral loads both systemically and the endocervic ...201627832025
use of injectable hormonal contraception and hsv-2 acquisition in a cohort of female sex workers in vancouver, canada.increased risk of herpes simplex virus 2 (hsv-2) has been proposed as a possible indirect pathway through which hormonal contraceptives (specifically depot medroxyprogesterone acetate (dmpa)) may increase the risk of hiv acquisition among women. we investigated the effects of dmpa on hsv-2 acquisition among female sex workers.201627821613
the effect of a conditional cash transfer on hiv incidence in young women in rural south africa (hptn 068): a phase 3, randomised controlled trial.cash transfers have been proposed as an intervention to reduce hiv-infection risk for young women in sub-saharan africa. however, scarce evidence is available about their effect on reducing hiv acquisition. we aimed to assess the effect of a conditional cash transfer on hiv incidence among young women in rural south africa.201627815148
incidence and risk factors for herpes simplex virus type 2 seroconversion among pregnant women in uganda: a prospective study.herpes simplex virus type 2 (hsv-2) acquired during pregnancy is associated with adverse outcomes such as perinatal hsv-2 transmission. hsv-2 seroconversion occurs within four weeks of hsv-2 acquisition. there was neither documented incidence nor risk factors for hsv-2 seroconversion during pregnancy in uganda. the objective of this study was to determine the incidence and risk factors for hsv-2 seroconversion among pregnant women in mulago hospital, uganda.201627801374
prevalence and determinants of hsv-2/syphilis co-infection and hsv-2 mono-infection among hiv-positive men who have sex with men: a cross-sectional study in northeast china.we aimed to assess the prevalence and determinants of herpes simplex virus type 2 (hsv-2) mono-infection and hsv-2/syphilis co-infection in human immunodeficiency virus (hiv)-positive men who have sex with men (msm) in china. a cross-sectional study was conducted on 545 hiv-positive msm in shenyang between february 2009 and october 2014. participants received physical examinations and serological tests for hsv-2 and syphilis. a multinomial logistic regression was used to identify risk factors as ...201627795468
rna-binding protein cpeb1 remodels host and viral rna landscapes.host and virus interactions occurring at the post-transcriptional level are critical for infection but remain poorly understood. here, we performed comprehensive transcriptome-wide analyses revealing that human cytomegalovirus (hcmv) infection results in widespread alternative splicing (as), shortening of 3' untranslated regions (3' utrs) and lengthening of poly(a)-tails in host gene transcripts. we found that the host rna-binding protein cpeb1 was highly induced after infection, and ectopic exp ...201627775709
seroprevalence and correlates of herpes simplex virus type 2 infection among young adults in arkhangelsk, northwest russia: a population-based cross-sectional study.herpes simplex virus type 2 (hsv-2) infection is the most common cause of genital ulcer disease (gud) worldwide. mother to child transmission causes high morbidity and mortality among infants. russia is on the brink of a generalized hiv-epidemic, but arkhangelsk is still a low-prevalence area. hsv-2 infection is associated with a three-fold increased risk of hiv-infection. the evidence on the seroprevalence of hsv-2 in russia is limited. the aim of this study was to assess hsv-2 seroprevalence a ...201627793121
herpes simplex virus type 2-associated recurrent aseptic meningitis (mollaret's meningitis) with a recurrence after 11-year interval: a case report.a 55-year-old woman was diagnosed with aseptic meningitis at the age of 43 and 44. she developed sudden fever and headache, and she showed nuchal rigidity. cerebrospinal fluid examination revealed pleocytosis (cell count 208/mm(3)) and was positive for herpes simplex virus type 2 (hsv-2) dna by pcr. acyclovir was started on the first day of admission, and she was complete recovery. preserved cerebrospinal fluid specimen from aseptic meningitis at the age of 44 was also positive for hsv-2 dna by ...201627773908
detection of virus in csf from the cases with meningoencephalitis by next-generation sequencing.we screened for viral dna in cerebrospinal fluid samples using next-generation sequencing (ngs) technology to diagnose cns viral infections. we collected csf samples from four cases with clinically suspected viral meningoencephalitis. dna extracted from the samples was analyzed with ngs, and the results were further validated using pcr. herpes simplex virus 1 (hsv-1) was detected in the csf of two patients, hsv-2 and human herpes virus type 3 (hhv-3, vzv) in the csf of two other patients separat ...201626506841
high expression level of antioxidants and pharmaceutical bioactivities of endophytic fungus chaetomium globosum jn711454.in order to maximize antioxidant activity of pharmaceutical bioactive endophytic fungus chaetomium globosum jn711454 during fermentation process, designed fermentation experiments of culture media for three levels of eight culture factors were performed using a taguchi orthogonal array (oa) design with layout l18 (2(1) × 3(7)). the agitation and the potato extract were the most significant affecting factors, and their interaction contributed significantly to fungus activity. the production of an ...201625569373
bovine herpesvirus type-1 glycoprotein k (gk) interacts with ul20 and is required for infectious virus production.we have previously shown that the hsv-1 gk and ul20 proteins interact and function in virion envelopment, membrane fusion, and neuronal entry. alignment of the predicted secondary structures of gks encoded by bohv-1, hsv-1, hsv-2, ehv-1 and vzv indicated a high degree of domain conservation. two bohv-1 gk-null mutant viruses were created by either gk gene deletion or stop codon insertion. in addition, a v5 epitope-tag was inserted at the carboxyl terminus of gk gene to detect gk. the engineered ...201627661734
prevalence and correlates of trichomonas vaginalis infection among female sex workers in a city in yunnan province, china.sexual transmission is the fastest growing route of hiv transmission in china, and trichomonas vaginalis(tv) can facilitate hiv transmission and acquisition. our goal was to determine the prevalence and correlates of tv infection among female sex workers (fsws). this cross-sectional study was conducted in a city of yunnan province in southern china, with confidential face-to-face interviews and laboratory tests for tv (wet mount) and other sexually transmitted infections. a total of 734 fsws par ...201625957327
[molecular detection of sexually transmitted agents in a symptomatic group of men and its relationship with sexual behavior].sexually transmitted infections (stis) affect sexual and reproductive health of millions of men. pathogens such as human papillomavirus (hpv), herpes simplex virus type 1 and 2 (hsv-1 y hsv-2), chlamydia trachomatis,mycoplasmagenitalium,mycoplasma hominis and ureaplasma urealyticum are associated with stis.201628112332
laryngopharyngeal reflux and herpes simplex virus type 2 are possible risk factors for adult-onset recurrent respiratory papillomatosis (prospective case-control study).the human papillomavirus (hpv) causes recurrent respiratory papillomatosis (rrp). although hpv prevalence is high, the incidence of papillomatosis is low. thus, factors other than hpv infection probably contribute to rrp. this study investigated whether patients with papillomatosis are more often infected with herpes simplex virus type 2 and chlamydia trachomatis (cht) and whether laryngopharyngeal reflux (lpr) occurs in this group of patients more often.201627759910
etiology of genital ulcer disease in male patients attending a sexually transmitted diseases clinic: first assessment in cuba.sexually transmitted diseases (stds) and in particular genital ulcer disease (gud) have a major impact on morbidity and mortality in developing countries. the world health organization recommends the use of syndromic guidelines for the treatment of sexually transmitted infections (stis) in resource-constrained countries. surveillance of autochthonous etiologies provides epidemiological information contributing to the prevention and treatment of stis. we investigated the etiology and factors asso ...201627419816
prevalence and risk factors of chlamydia trachomatis, neisseria gonorrhoeae, trichomonas vaginalis and other sexually transmissible infections among women attending antenatal clinics in three provinces in papua new guinea: a cross-sectional survey.background: papua new guinea (png) is estimated to have among the highest prevalences of hiv and sexually transmissible infections (stis) of any asia-pacific country, and one of the highest burdens of maternal syphilis globally. the prevalence of curable stis, such as chlamydia trachomatis (ct), neisseria gonorrhoeae (ng) and trichomonas vaginalis (tv), among pregnant women in png is relatively unknown. methods: a cross-sectional bio-behavioural survey to investigate the epidemiology of ct, ng, ...201627248708
the influence of hormonal factors on the risk of developing cervical cancer and pre-cancer: results from the epic cohort.in addition to hpv, high parity and hormonal contraceptives have been associated with cervical cancer (cc). however, most of the evidence comes from retrospective case-control studies. the aim of this study is to prospectively evaluate associations between hormonal factors and risk of developing cervical intraepithelial neoplasia grade 3 (cin3)/carcinoma in situ (cis) and invasive cervical cancer (icc).201626808155
hiv/sexually transmitted infection prevention messaging: targeting root causes of sexual risk behavior.sexual risk behaviors (srbs) often lead to sexually transmitted infections (sti), yet little is known about what drives srb and whether this differs by sex.201626760178
multiplex pcr testing for nine different sexually transmitted infections.current sexually transmitted infection (sti) testing is not optimal due to delays in reporting or missed diagnoses due to a lack of comprehensive testing. the filmarray® (biofire diagnostics, llc, salt lake city, utah) is a user-friendly, fully automated, multiplex pcr system that is being developed for rapid point-of-care use. a research-use-only sti panel including multiple pcr primer sets for each organism was designed to detect chlamydia trachomatis, neisseria gonorrhoeae, treponema pallidum ...201626538551
herpes simplex virus (hsv) modulation of staphylococcus aureus and candida albicans initiation of hela 299 cell-associated biofilm.although herpes simplex virus type-1 (hsv-1), and type-2 (hsv-2), staphylococcus aureus and candida albicans co-habit the oral and genital mucosa, their interaction is poorly understood. we determined the effect hsv has on bacterial and/or fungal adherence, the initial step in biofilm formation. hela229 cells were infected with hsv-1 (kos) gl86 or hsv-2 (kos) 333gj (-) at a multiplicity of infection (moi) of 50 and 10. s. aureus (atcc 25923) and/or c. albicans (yeast forms or germ tube forms) we ...201626758707
decrease in seroprevalence for herpesviruses among pregnant women in finland: cross-sectional study of three time points 1992, 2002 and 2012.maternal herpesvirus infections during pregnancy may cause fetal and neonatal infections. we investigated the seroprevalence of five herpesviruses: cytomegalovirus (cmv), herpes simplex virus (hsv) 1 and 2, varicella zoster virus (vzv) and epstein-barr virus (ebv) in randomly selected samples from pregnant finnish women from the years 1992, 2002 and 2012. over 20 years, the seroprevalences decreased significantly for cmv from 84.5% to 71.5% (p = 0.007) and hsv-1 from 69.5% to 45% (p < 0.001). th ...201626654892
immunological signaling during herpes simplex virus-2 and cytomegalovirus vaginal shedding after initiation of antiretroviral treatment.vaginal proinflammatory cytokine expression during herpes virus reactivation was examined in human immunodeficiency virus-infected women before and after initiation of antiretroviral therapy (art). vaginal swabs were screened for levels of cytokines interleukin (il)-1β, il-2, il-4, il-6, il-8, il-10, il-12p70, il-13, tumor necrosis factor (tnf)-α, and interferon-γ. the relative risk (rr) of herpes simplex virus-2 or cytomegalovirus (cmv) shedding being associated with cytokine levels above the m ...201627191006
[immune system data in patients with persistent recurent herpes virus infections in dynamics of complex therapy].the positive clinical, serolgical and immunological effects of glutamyl-triptophan in patients on persistent herpes virus infections are shown. treatment resulted in the increase of avidity on hsv 1, hsv 2, cmv, ebv antibody, the levels of cd3+-, icd8+-, cd16+-, cd3+hla-dr+- (%, abs) and.cd3+cd25t-cells (%), that indicates the optimization of the immune systemdata. the data received allow to recommend bestim for patients with persistent herpes virus infections.201627089710
seroprevalence of cmv, hsv-2 and hbv among hiv-infected malawian children: a cross-sectional survey.little is known about viral co-infections in african human immunodeficiency virus (hiv)-infected children. we examined the prevalence of seromarkers for cytomegalovirus (cmv), herpes simplex virus type 2 (hsv-2) and hepatitis b virus (hbv) infections among hiv-infected, antiretroviral treatment (art)-naïve children in lilongwe, malawi.201626884443
exposure to perinatal infections and bipolar disorder: a systematic review.bipolar disorder (bd) is a debilitating psychiatric disorder and a growing global public health issue. notwithstanding bd has been conceptualized as a neuroprogressive illness, there are some evidences to suggest a role for neurodevelopmental pathways in the patho-etiology of this disorder. evidences on the associations between perinatal infections and risk for bipolar disorder have been inconsistent across studies. here, we performed a systematic review of observational studies on the relations ...201626812921
common infections with polyomaviruses and herpesviruses and neuropsychological development at 4 years of age, the rhea birth cohort in crete, greece.viral infections of the central nervous system may have detrimental effects for the developing brain, but the effects of less virulent common infections are unclear. we aim to investigate the impact of common viral infections of early childhood on neuropsychological performance of children at age four.201627334233
shedding of hsv-1, hsv-2, cmv, and ebv in the saliva of hematopoietic stem cell transplant recipients at fundación homi - hospital de la misericordia, bogotá, d.c.hematopoietic stem cell transplantation in pediatric patients is an alternative treatment for different diseases. the conditioning regimen for transplant predisposes recipients to the development of infections. viral infections by herpes simplex virus 1 (hsv-1), herpes simplex virus 2 (hsv-2), human cytomegalovirus (cmv), and epstein-barr virus (ebv), are the most common, and the leading cause of morbidity and mortality among these patients. these viruses lie dormant in various cell types and th ...201627622810
the role of human papilloma virus and herpes viruses in the etiology of nasal polyposis.the aim of this study was to investigate the etiological role of human papilloma virus (hpv), herpes simplex virus (hsv), varicella-zoster virus (vzv), epstein-barr virus (ebv), cytomegalovirus (cmv), and human herpes virus-6 (hhv-6) and -7 (hhv-7) in the occurrence of nasal polyposis.201627511490
immunohistochemistry is rarely justified for the diagnosis of viral infections.to determine the utility of immunohistochemistry (ihc) for the diagnosis of viral infections in surgical pathology specimens lacking characteristic viral cytopathic effects.201628007703
oral shedding of human herpesviruses in patients undergoing radiotherapy/chemotherapy treatment for head and neck squamous cell carcinoma.opportunistic infections may affect the oral mucosa of patients undergoing radio/chemotherapy through exacerbation of oral mucositis. the aim of this study is to evaluate the oral shedding of all eight human herpesviruses and its possible association with oral mucositis.201627966015
simultaneous quantification of the 8 human herpesviruses in allogeneic hematopoietic stem cell transplantation.human herpesviruses may cause severe complications after allogeneic hematopoietic stem cell transplantation (hsct). however, the impact of some of these infections on transplant outcomes is still unclear. a prospective survey on the incidence and clinical features of herpesviruses infections after hsct has not yet been conducted in brazilian patients, and the impact of these infections on hsct outcome remains unclear.201626555946
correlating flavivirus virulence and levels of intrinsic disorder in shell proteins: protective roles vs. immune evasion.computational analyses revealed correlations between the intrinsic disorder propensity of shell proteins and case fatality rates (cfrs) among flaviviruses and within at least two flavivirus species, such as tick-borne encephalitis virus (tbev) and dengue virus (denv). the shell proteins analyzed in this study are capsid (c) and membrane (prm, pr, and m) proteins. the highest correlations can be found when regression analyses were conducted using pr (flavivirus: r(2) = 0.78, p < 0.01) or m (flavi ...201627102744
comparison of follicular and luteal phase mucosal markers of hiv susceptibility in healthy women.the purpose of this study was to evaluate differences in vaginal immune cell populations, vaginal tissue gene expression, antimicrobial activity of the cervicovaginal (cv) lavage (cvl), vaginal flora, and p24 antigen production from cv tissues after ex vivo human immunodeficiency virus (hiv) infection between follicular (fol) and luteal (lut) phases of the menstrual cycle. cv tissue biopsies, cv secretions, and blood samples were obtained as part of two longitudinal clinical trials of healthy wo ...201626750085
does place of service matter? a utilisation and cost analysis of sexually transmissible infection testing from 2012 claims data.background in this study, a previous study on the utilisation and cost of sexually transmissible infection (sti) tests was augmented by focusing on outpatient place of service for the most utilised tests.201626774890
parallel declines in hiv and hepatitis c virus prevalence, but not in herpes simplex virus type 2 infection: a 10-year, serial cross-sectional study in an inner-city emergency department.the johns hopkins hospital emergency department (jhhed) has served as an observational window on the hiv epidemic in a socioeconomically depressed, urban population. we previously reported that hiv incidence among jhhed patients is decreasing and that prevalence has declined from 11.4% in 2003-5.6% in 2013.201627232485
high prevalence of herpes simplex virus (hsv)- type 2 co-infection among hiv-positive women in ukraine, but no increased hiv mother-to-child transmission risk.over 3500 hiv-positive women give birth annually in ukraine, a setting with high prevalence of sexually transmitted infections. herpes simplex virus type 2 (hsv-2) co-infection may increase hiv mother-to-child transmission (mtct) risk. we explored factors associated with hsv-2 seropositivity among hiv-positive women in ukraine, and its impact on hiv mtct.201627121953
in vitro and in vivo antiherpetic effects of (1r,2r)-1-(5'-methylful-3'-yl)propane-1,2,3-triol.in this study, we demonstrated the in vitro and in vivo antiherpetic activities of a stable furan derivative, (1r,2r)-1-(5'-methylful-3'-yl)propane-1,2,3-triol (mfpt), which had originally been isolated from streptomyces sp. strain fv60. in the present study, we synthesized mfpt from (5-methylfuran-3-yl)methanol in 6 steps for use in the experiments. mfpt showed potent in vitro antiviral activities against two acyclovir (acv)-sensitive (kos and hf) strains and an acv-resistant (a4-3) strain of h ...201626763002
false-negative type-specific glycoprotein g antibody responses in sti clinic patients with recurrent hsv-1 or hsv-2 dna positive genital herpes, the netherlands.herpes simplex virus (hsv) type-discriminating antibody tests (glycoprotein g (gg) directed) are used to identify naïve persons and differentiate acute infections from recurrences. we studied test characteristics of three commercially available antibody tests in patients with recurrent (established by viral pcr tests) herpes simplex virus type 1 (hsv-1) or herpes simplex virus type 2 (hsv-2) genital herpes episodes.201626755775
herpes simplex virus encephalitis in peru: a multicentre prospective study.herpes simplex virus (hsv) is one of the most commonly identified infectious aetiologies of encephalitis in north america and europe. the epidemiology of encephalitis beyond these regions, however, is poorly defined. during 2009-2012 we enrolled 313 patients in a multicentre prospective study of encephalitis in peru, 45 (14·4%) of whom had confirmed hsv infection. of 38 patients with known hsv type, 84% had hsv-1 and 16% had hsv-2. patients with hsv infection were significantly more likely to pr ...201626733400
herpes simplex type 2 encephalitis after craniotomy: case report and literature review.herpes simplex encephalitis (hse) after neurosurgical procedures is extremely uncommon, and the few published case reports mainly described herpes simplex virus type 1 (hsv-1) as being culpable. we present a rare case of hsv-2 encephalitis after craniotomy and describe its pathophysiology and optimal management.201626724620
development of a multiplex real-time pcr for the simultaneous detection of herpes simplex and varicella zoster viruses in cerebrospinal fluid and lesion swab specimens.herpes simplex viruses (hsv) and varicella zoster virus (vzv) can have very similar and wide-ranging clinical presentations. rapid identification is necessary for timely antiviral therapy, especially with infections involving the central nervous system, neonates, and immunocompromised individuals. detection of hsv-1, hsv-2 and vzv was combined into one real-time pcr reaction utilizing hydrolysis probes. the assay was validated on the lightcycler(®) (roche) and applied biosystems 7500 real-time p ...201626711555
antiviral activity of hatay propolis against replication of herpes simplex virus type 1 and type 2.background propolis is a bee product widely used in folk medicine and possessing many pharmacological properties. in this study we aimed to investigate: i) the antiviral activities of hatay propolis samples against hsv-1 and hsv-2 in hep-2 cell line, and ii) the presence of the synergistic effects of propolis with acyclovir against these viruses. material and methods all experiments were carried out in hep-2 cell cultures. proliferation assays were performed in 24-well flat bottom microplates. w ...201626856414
the agma1 poly(amidoamine) inhibits the infectivity of herpes simplex virus in cell lines, in human cervicovaginal histocultures, and in vaginally infected mice.the development of topical microbicides is a valid approach to protect the genital mucosa from sexually transmitted infections that cannot be contained with effective vaccination, like hsv and hiv infections. a suitable target of microbicides is the interaction between viral proteins and cell surface heparan sulfate proteoglycans (hspgs). agma1 is a prevailingly cationic agmatine-containing polyamidoamine polymer previously shown to inhibit hspgs dependent viruses, including hsv-1, hsv-2, and hp ...201626854390
characterization of the c-terminal nuclease domain of herpes simplex virus pul15 as a target of nucleotidyltransferase inhibitors.the natural product α-hydroxytropolones manicol and β-thujaplicinol inhibit replication of herpes simplex viruses 1 and 2 (hsv-1 and hsv-2, respectively) at nontoxic concentrations. because these were originally developed as divalent metal-sequestering inhibitors of the ribonuclease h activity of hiv-1 reverse transcriptase, α-hydroxytropolones likely target related hsv proteins of the nucleotidyltransferase (ntase) superfamily, which share an "rnase h-like" fold. one potential candidate is pul1 ...201626829613
broad and potent antiviral activity of the nae inhibitor mln4924.in terms of infected human individuals, herpesviruses range among the most successful virus families. subclinical herpesviral infections in healthy individuals contrast with life-threatening syndromes under immunocompromising and immunoimmature conditions. based on our finding that cytomegaloviruses interact with cullin roc ubiquitin ligases (crls) in the context of interferon antagonism, we systematically assessed viral dependency on crls by utilizing the drug mln4924. crl activity is regulated ...201626829401
high conservation of herpes simplex virus ul5/ul52 helicase-primase complex in the era of new antiviral therapies.the emergence of herpes simplex virus (hsv) resistance to current antiviral drugs, that all target the viral dna polymerase, constitutes a major obstacle to antiviral treatment effectiveness of hsv infections, especially in immunocompromised patients. a novel and promising class of inhibitors of the hsv ul5/ul52 helicase-primase (hp) complex has been reported to hinder viral replication with a high potency. in this study, we describe the low natural polymorphism (interstrain identity >99.1% at b ...201626826441
h2ax phosphorylation and dna damage kinase activity are dispensable for herpes simplex virus replication.herpes simplex virus type 1 (hsv-1) can establish both lytic and latent infections in humans. the phosphorylation of histone h2ax, a common marker of dna damage, during lytic infection by hsv-1 is well established. however, the role(s) of h2ax phosphorylation in lytic infection remain unclear.201626817608
synthetic α-hydroxytropolones inhibit replication of wild-type and acyclovir-resistant herpes simplex viruses.herpes simplex virus 1 (hsv-1) and hsv-2 remain major human pathogens despite the development of anti-hsv therapeutics as some of the first antiviral drugs. current therapies are incompletely effective and frequently drive the evolution of drug-resistant mutants. we recently determined that certain natural troponoid compounds such as β-thujaplicinol readily suppress hsv-1 and hsv-2 replication. here, we screened 26 synthetic α-hydroxytropolones with the goals of determining a preliminary structu ...201626787704
conserved tryptophan motifs in the large tegument protein pul36 are required for efficient secondary envelopment of herpes simplex virus capsids.herpes simplex virus (hsv) replicates in the skin and mucous membranes, and initiates lytic or latent infections in sensory neurons. assembly of progeny virions depends on the essential large tegument protein pul36 of 3,164 amino acid residues that links the capsids to the tegument proteins pul37 and vp16. of the 32 tryptophans of hsv-1-pul36, the tryptophan-acidic motifs (1766)wd(1767) and (1862)we(1863) are conserved in all hsv-1 and hsv-2 isolates. here, we characterized the role of these mot ...201627009950
in vitro studies of the antiherpetic effect of photodynamic therapy.the number of viral infection cases in the department of gynecology and obstetrics has tended to increase over last few years. viruses form herpesvirus and cytomegalovirus families are associated with an increased risk for recurrent pregnancy loss. photodynamic therapy (pdt) is a promising new approach to treat viral infections in which viral particles are inactivated. it exhibits great therapeutic potential, particularly among this group of patients. this study examined the use of pdt to treat ...201627003896
status of vaccine research and development of vaccines for herpes simplex virus.herpes simplex virus type-1 (hsv-1) and -2 (hsv-2) are highly prevalent global pathogens which commonly cause recurrent oral and genital ulcerations. less common but more serious complications include meningitis, encephalitis, neonatal infection, and keratitis. hsv-2 infection is a significant driver of the hiv epidemic, increasing the risk of hiv acquisition 3 fold. as current control strategies for genital hsv-2 infection, including antiviral therapy and condom use, are only partially effectiv ...201626973067
polyhydroxylated sulfated steroids derived from 5α-cholestanes as antiviral agents against herpes simplex virus.twelve polyhydroxylated sulfated steroids synthesized from a 5α-cholestane skeleton with different substitutions in c-2, c-3 and c-6 were evaluated for cytotoxicity and antiviral activity against herpes simplex virus (hsv) by a virus plaque reduction assay. four compounds elicited a selective inhibitory effect against hsv. the disodium salt of 2β,3α-dihydroxy-6e-hydroximine-5α-cholestane-2,3-disulfate, named compound 7, was the most effective inhibitor of hsv-1, hsv-2 and pseudorabies virus (prv ...201627101075
implementation and evaluation of a fully automated multiplex real-time pcr assay on the bd max platform to detect and differentiate herpesviridae from cerebrospinal fluids.a fully automated multiplex real-time pcr assay--including a sample process control and a plasmid based positive control--for the detection and differentiation of herpes simplex virus 1 (hsv1), herpes simplex virus 2 (hsv2) and varicella-zoster virus (vzv) from cerebrospinal fluids (csf) was developed on the bd max platform. performance was compared to an established accredited multiplex real time pcr protocol utilizing the easymag and the lightcycler 480/ii, both very common devices in viral mo ...201627092772
managing atypical and typical herpetic central nervous system infections: results of a multinational study.there have been many studies pertaining to the management of herpetic meningoencephalitis (hme), but the majority of them have focussed on virologically unconfirmed cases or included only small sample sizes. we have conducted a multicentre study aimed at providing management strategies for hme. overall, 501 adult patients with pcr-proven hme were included retrospectively from 35 referral centres in 10 countries; 496 patients were found to be eligible for the analysis. cerebrospinal fluid (csf) a ...201627085724
atypical vzv retinitis in a patient with good syndrome.to describe atypical varicella zoster virus (vzv) retinitis in a patient with good syndrome.201627494574
herpes simplex virus type 1 and type 2 in the netherlands: seroprevalence, risk factors and changes during a 12-year period.genital herpes results in considerable morbidity, including risk of neonatal herpes, and is increasingly being caused by herpes simplex virus (hsv) type 1. possibly children are less often hsv-1 infected, leaving them susceptible until sexual debut. we assessed changes in the dutch hsv-1 and hsv-2 seroprevalence over time and determinants associated with hsv seropositivity.201627484304
3,19-isopropylideneandrographolide suppresses early gene expression of drug-resistant and wild type herpes simplex viruses.a diterpenoid lactone, 3,19-isopropylideneandrographolide (ipad) compound isolated from andrographis paniculata (burm. f.) nees, has been reported to inhibit herpes simplex virus type 1 (hsv-1) infection at the post-entry step. to identify the molecular target of ipad, this study characterized the inhibitory effect of ipad on infection of vero cells by hsv-1, hsv-2 and a drug-resistant (dr) hsv-1 strain acgr4 (acyclovir-resistant and thymidine kinase (tk)-deficient). viral production, gene and p ...201627424493
antiherpetic plants: a review of active extracts, isolated compounds, and bioassays.herpes simplex is a disease that is widely distributed throughout the world. it is caused by herpes simplex virus type 1 (hsv-1) and simplex virus type 2 (hsv-2). the drugs of choice for treatment are acyclovir (acv), penciclovir (pcv) and other guanine analogues, which have the same mechanism of action. however, due to the constant increase of acv-resistant strains in immunocompromised patients, it is necessary to find new treatment alternatives. it has been shown that natural products are a go ...201627396217
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, ...201627362483
inhibition of herpes simplex type 1 and type 2 infections by oximacro(®), a cranberry extract with a high content of a-type proanthocyanidins (pacs-a).in the absence of efficient preventive vaccines, topical microbicides offer an attractive alternative in the prevention of herpes simplex type 1 (hsv-1) and type 2 (hsv-2) infections. because of their recognized anti-adhesive activity against bacterial pathogens, cranberry (vaccinium macrocarpon ait.) extracts may represent a natural source of new antiviral microbicides. however, few studies have addressed the applications of cranberry extract as a direct-acting antiviral agent. here, we report ...201627321663
csf herpes virus and autoantibody profiles in the evaluation of encephalitis.to report the frequency of coexisting herpes viruses (herpes simplex virus 1 [hsv-1] or hsv-2, varicella zoster virus, epstein-barr virus [ebv], cytomegalovirus, or human herpes virus 6 [hhv-6]) and autoantibodies in patients with encephalitis (herpes or autoimmune) in clinical laboratory service.201627308306
antiviral activity of myticin c peptide from mussel: an ancient defense against herpesviruses.little is known about the antiviral response in mollusks. as in other invertebrates, the interferon signaling pathways have not been identified, and in fact, there is a debate about whether invertebrates possess antiviral immunity similar to that of vertebrates. in marine bivalves, due to their filtering activity, interaction with putative pathogens, including viruses, is very high, suggesting that they should have mechanisms to address these infections. in this study, we confirmed that constitu ...201627307570
mathematical modeling predicts that increased hsv-2 shedding in hiv-1 infected persons is due to poor immunologic control in ganglia and genital mucosa.a signature feature of hiv infection is poor control of herpes virus infections, which reactivate from latency and cause opportunistic infections. while the general mechanism underlying this observation is deficient cd4+t-cell function, it is unknown whether increased severity of herpes virus infections is due primarily to poor immune control in latent or lytic sites of infection, or whether cd4+ immunodeficiency leads to more critical downstream deficits in humoral or cell-mediated immunologic ...201627285483
genital herpes: a review.genital herpes is a common sexually transmitted disease, affecting more than 400 million persons worldwide. it is caused by herpes simplex virus (hsv) and characterized by lifelong infection and periodic reactivation. a visible outbreak consists of single or clustered vesicles on the genitalia, perineum, buttocks, upper thighs, or perianal areas that ulcerate before resolving. symptoms of primary infection may include malaise, fever, or localized adenopathy. subsequent outbreaks, caused by react ...201627281837
exocytosis of alphaherpesvirus virions, light particles, and glycoproteins uses constitutive secretory mechanisms.many molecular and cell biological details of the alphaherpesvirus assembly and egress pathway remain unclear. recently we developed a live-cell fluorescence microscopy assay of pseudorabies virus (prv) exocytosis, based on total internal reflection fluorescence (tirf) microscopy and a virus-encoded ph-sensitive fluorescent probe. here, we use this assay to distinguish three classes of viral exocytosis in a nonpolarized cell type: (i) trafficking of viral glycoproteins to the plasma membrane, (i ...201627273828
the role of micrornas in the pathogenesis of herpesvirus infection.micrornas (mirnas) are small non-coding rnas important in gene regulation. they are able to regulate mrna translation through base-pair complementarity. cellular mirnas have been involved in the regulation of nearly all cellular pathways, and their deregulation has been associated with several diseases such as cancer. given the importance of micrornas to cell homeostasis, it is no surprise that viruses have evolved to take advantage of this cellular pathway. viruses have been reported to be able ...201627271654
development of a high-throughput β-gal-based neutralization assay for quantitation of herpes simplex virus-neutralizing antibodies in human samples.measurement of neutralizing antibodies against herpes simplex virus (hsv) is important for evaluation of candidate vaccines. the established plaque-reduction neutralization assay is time consuming, labor intensive, and difficult to validate and transfer. here, we describe the characterization of a hsv-neutralization assay based on the expression of a reporter gene, β-galactosidase (β-gal). using previously constructed hsv-β-gal recombinant viruses, hsv-2/gal and hsv-1/tk12, we developed a colori ...201627265458
herpes simplex virus type 1 and type 2 infection increases atherosclerosis risk: evidence based on a meta-analysis.objective. the aim of our study was to evaluate the relation of herpes simplex virus type 1 (hsv-1) and type 2 (hsv-2) infection with the risk of atherosclerosis (as). methods. a systematic literature search was performed through three electronic databases. the pooled odds ratio (or) and corresponding 95% confidence interval (ci) were used to assess the effect of hsv-1 and hsv-2 infection on as risk. results. 17 studies were available for meta-analysis of hsv-1 infection and as risk and seven st ...201627195284
herpes simplex virus-2 esophagitis in a young immunocompetent adult.herpes simplex esophagitis (hse) is commonly identified in immunosuppressed patients. it is rare among immunocompetent patients and almost all of the reported cases are due to hsv-1 infection. hsv-2 esophagitis is extremely rare. we report the case of a young immunocompetent male who presented with dysphagia, odynophagia, and epigastric pain. endoscopy showed multitudes of white nummular lesions in the distal esophagus initially suspected to be candida esophagitis. however, classic histopatholog ...201627195158
multicenter evaluation of meridian bioscience hsv 1&2 molecular assay for detection of herpes simplex virus 1 and 2 from clinical cutaneous and mucocutaneous specimens.herpes simplex virus (hsv) causes acute and relapsing symptoms characterized by ulcerative lesions. laboratory diagnosis of hsv in cutaneous or mucocutaneous lesions has historically been performed with the use of viral cell culture systems; however, these tests are laborious and suffer decreased sensitivity for advanced-stage lesions. the recent availability of fda-cleared moderately complex assays has resulted in the increased use of molecular diagnostics for the routine detection of hsv in su ...201627194690
development and evaluation of a host-targeted antiviral that abrogates herpes simplex virus replication through modulation of arginine-associated metabolic pathways.since their inception five decades ago, most antivirals have been engineered to disrupt a single viral protein or process that is essential for viral replication. this approach has limited the overall therapeutic effectiveness and applicability of current antivirals due to restricted viral specificity, a propensity for development of drug resistance, and an inability to control deleterious host-mediated inflammation. as obligate intracellular parasites, viruses are reliant on host metabolism and ...201627192555
performance of the hsv oligogen kit for the diagnosis of herpes simplex virus type 1 and 2.pcr methods are nowadays between the most rapid and sensitive methods for screening and diagnosing herpes simplex virus (hsv) type 1 and 2. the aim of this study was to analyze the reliability, accuracy, and usefulness of the new assay hsv oligogen kit in comparison with the roche lightcycler hsv ½ qual kit assay for the detection of hsv in clinical samples. for this analysis, a prospective study was designed for detection of hsv-1 and hsv-2 including 110 ulcer specimens, 48 urine, 48 endocervic ...201627185644
prevalence of intrathecal acyclovir resistant virus in herpes simplex encephalitis patients.herpes simplex encephalitis (hse) is a life-threatening complication of herpes simplex virus (hsv) infection. acyclovir (acv) is the antiviral treatment of choice, but may lead to emergence of acv-resistant (acvr) hsv due to mutations in the viral ul23 gene encoding for the acv-targeted thymidine kinase (tk) protein. here, we determined the prevalence of intrathecal acvr-associated hsv tk mutations in hse patients and compared tk genotypes of sequential hsv isolates in paired cerebrospinal fluid ...201627171421
herpesvirus infections and risk of frailty and mortality in older women: women's health and aging studies.to examine the relationship between herpesvirus infections and mortality and incident frailty risks in community-dwelling older women.201627131018
an escalating dose study to assess the safety, tolerability and immunogenicity of a herpes simplex virus dna vaccine, cor-1.this paper describes a single site, open-label phase i clinical trial evaluating the safety, tolerability and immunogenicity in healthy volunteers of a herpes simplex polynucleotide vaccine that has previously been shown to enhance immunogenicity and protect against lethal herpes simplex virus type 2 (hsv-2) challenge in mice. five escalating doses of the vaccine, cor-1, were given by intradermal injection to hsv-1 and 2 seronegative healthy individuals. cor-1 was found to be safe and well-toler ...201627580249
hsv-2 δgd elicits fcγr-effector antibodies that protect against clinical isolates.a single-cycle herpes simplex virus (hsv) deleted in glycoprotein d (δgd-2) elicited high titer hsv-specific antibodies (abs) that (i) were rapidly transported into the vaginal mucosa; (ii) elicited antibody-dependent cell-mediated cytotoxicity but little neutralization; (iii) provided complete protection against lethal intravaginal challenge; and (iv) prevented establishment of latency in mice. however, clinical isolates may differ antigenically and impact vaccine efficacy. to determine the bre ...201627536733
structural characterization and antiviral effect of a novel polysaccharide psp-2b from prunellae spica.in the present study, a novel polysaccharide, psp-2b, was isolated from aqueous extracts of prunellae spica by direct ultrafiltration membrane separation and gel chromatography purification. psp-2b is a partially sulphated polysaccharide with a molecular weight of approximately 32kda. its sulfate content is 10.59% by elemental analysis. the major sugars comprising psp-2b are arabinose, galactose and mannose, in addition to small amounts of glucose and uronic acids. the framework of psp-2b is spe ...201627516321
b virus (macacine herpesvirus 1) divergence: variations in glycoprotein d from clinical and laboratory isolates diversify virus entry strategies.b virus (macacine herpesvirus 1) can cause deadly zoonotic disease in humans. molecular mechanisms of b virus cell entry are poorly understood for both macaques and humans. here we investigated the abilities of clinical b virus isolates to use entry receptors of herpes simplex viruses (hsv). we showed that resistant b78h1 cells became susceptible to b virus clinical strains upon expression of either human nectin-2 or nectin-1. antibody against glycoprotein d (gd) protected these nectin-bearing c ...201627512063
adenovirus-mediated shrna interference against hsv-1 replication in vitro.the ul29 and ul28 proteins encoded by herpes simplex virus type 1 (hsv-1) are critical for its replication and packaging, respectively. research has demonstrated that synthesized sirna molecules targeting the ul29 gene are able to suppress hsv-2 replication and the ul28-null hsv-1 gene cannot form infectious viruses in vitro. silencing the ul28 and ul29 genes by rnai might lead to the development of novel antiviral agents for the treatment of hsv-1 infections. two kinds of short hairpin rnas (sh ...201627566181
seroprevalence and co-infection of human immunodeficiency virus (hiv) and herpes simplex virus (hsv) among pregnant women in lokoja, north-central nigeria.herpes simplex virus 1 (hsv-1) is normally associated with orofacial (orolabial) infections and encephalitis, whereas hsv-2 usually causes genital infections and can be transmitted from infected mothers to neonates. the evidence suggesting that hsv is facilitating the spread of the global human immunodeficiency virus (hiv) epidemic and the risk posed by these synergies to neonates in developing countries informed this study.201628180012
erratum: increased expression of herpes virus-encoded hsv1-mir-h18 and hsv2-mir-h9-5p in cancer-containing prostate tissue compared to that in benign prostate hyperplasia tissue.[this corrects the article on p. 122 in vol. 20, pmid: 27377944.].201628043100
serologic screening for genital herpes infection: us preventive services task force recommendation statement.genital herpes is a prevalent sexually transmitted infection in the united states, occurring in almost 1 in 6 persons aged 14 to 49 years. infection is caused by 2 subtypes of the herpes simplex virus (hsv), hsv-1 and hsv-2. antiviral medications may provide symptomatic relief from outbreaks but do not cure hsv infection. neonatal herpes infection, while uncommon, can result in substantial morbidity and mortality.201627997659
the prevalence of herpes simplex virus type 1 and 2 infection in iran: a meta-analysis.seroepidemiologic studies indicate a high prevalence of herpes simplex virus (hsv) infection. this infection leads to ophthalmic, dermatologic, oral, neurologic, vaginal and cervical problems. different studies have been carried out to estimate the hsv seroprevalence in iran. combining the results of these studies would be useful for health policy-making.201627921084
herpes simplex virus specific t cell response in a cohort with primary genital infection correlates inversely with frequency of subsequent recurrences.during the last decades, a changing epidemiological pattern of genital herpes simplex virus (hsv) infection has emerged. primary infection is now caused as often by hsv-1 as by hsv-2. once established, hsv can be reactivated leading to recurrent mucocutaneous lesions as well as meningitis. why some otherwise immune-competent individuals experience severe and frequent recurrences is not known, and the immunological mechanism underlying recurrent symptomatic hsv infection is not fully understood. ...201627903680
maternal antibodies to herpes virus antigens and risk of gastroschisis in offspring.gastroschisis risk is highest in offspring of young women and is increasing in prevalence, suggesting that exposures that are increasingly common among younger females may be causal. some infections by viruses in the herpes family are more common in the earlier childbearing years and have been increasing in prevalence over time. data from the finnish maternity cohort were linked to finnish malformation and birth registers (1987-2012) for this study, a nested case-control study of mothers of offs ...201627856447
associations between excessive adiposity and seroprevalence of herpes simplex virus type 1 and type 2 among us adults: a population-based age-period-cohort analysis.evidence on the association between herpes simplex virus (hsv) and excessive adiposity, such as obesity (body mass index ≥30 kg/m(2)) and abdominal obesity (waist circumference (wc) >102 or 88 cm), has been inconsistent. we sought to examine whether age-period-cohort (apc) effects could explain for the observed heterogeneities.201627798014
type-specific detection of herpes simplex virus type 1 and type 2 using the cobas® hsv 1 and 2 test on the cobas® 4800 platform.hsv-1 and hsv-2 are among the most common causes of sexually transmitted infections (stis) globally. these infections are strongly associated with increased risk of hiv acquisition and rare, but devastating, neonatal disease. available treatment options can reduce hsv transmission and improve quality of life. accurate diagnosis early in disease can improve patient management. areas covered: this paper describes the clinical manifestations of hsv infection often used for clinical diagnostic purpo ...201627687862
α herpes virus infections among renal transplant recipients.the α herpes viruses hsv-1, hsv-2, and vzv often reactivate in the setting of immune suppression after solid organ transplantation. oral or genital mucocutaneous disease is the most common clinical manifestation of hsv disease while vzv manifests as varicella (or chickenpox) or reactivation herpes zoster, characterized by a diffuse rash, or a painful unilateral vesicular eruption in a dermatomal distribution, respectively. the diagnosis of hsv and vzv is primarily based on history and clinical p ...201627772619
multicenter evaluation of the luminex® aries® hsv 1&2 assay for the detection of herpes simplex virus types 1 and 2 in cutaneous and mucocutaneous lesion specimens.the aries® hsv 1&2 assay is a new fda cleared real-time pcr test for detection and differentiation of hsv-1 and hsv-2 dna from cutaneous and mucocutaneous lesions. the test is performed on the aries® system, an automated sample to answer real-time pcr instrument that provides a closed system and simple workflow for performing molecular testing. areas covered: this article reports the clinical performance of the aries® hsv 1&2 assay assessed on 1963 prospectively collected specimens. assay sensit ...201627771977
altered gene expression of glycosyltransferases and sialyltransferases and total amount of glycosphingolipids following herpes simplex virus infection.there is a case report of a patient with overlapping guillain-barré syndrome and bickerstaff brainstem encephalitis after infection with herpes simplex virus type 1 (hsv-1), who carried high titers of serum anti-gq1b igg antibodies. several studies have linked viral infection to the modulation of ganglioside expression such as human t-lymphotropic virus to gd2 and simian virus 40 to gm3. also, enhancement of the expression of gm2 on the cell membrane after cytomegalovirus infection has been repo ...201627588895
the unexpected detection of varicella-zoster virus in genital specimens using the lyra™ direct hsv 1+2/vzv assay.the lyra™ direct hsv 1+2/vzv assay is a moderately complex, multiplex pcr assay that qualitatively detects the presence of hsv 1, hsv 2, and vzv dna in cutaneous and mucocutaneous specimens with a time-to-result of less than 60min.201627756008
anti-hsv activity of kuwanon x from mulberry leaves with genes expression inhibitory and hsv-1 induced nf-κb deactivated properties.six stilbene derivatives isolated from mulberry leaves including kuwanon x, mulberrofuran c, mulberrofuran g, moracin c, moracin m 3'-o-b-glucopyranoside and moracin m were found to have antiviral effects against herpes simplex virus type 1 and 2 (hsv-1 and hsv-2) at different potencies except for mulberrofuran g. kuwanon x exhibited the greatest activity against hsv-1 15577 and clinical strains and hsv-2 strain 333 with ic50 values of 2.2, 1.5 and 2.5 µg/ml, respectively. further study revealed ...201627725444
distribution and effects of amino acid changes in drug-resistant α and β herpesviruses dna polymerase.emergence of drug-resistance to all fda-approved antiherpesvirus agents is an increasing concern in immunocompromised patients. herpesvirus dna polymerase (dnapol) is currently the target of nucleos(t)ide analogue-based therapy. mutations in dnapol that confer resistance arose in immunocompromised patients infected with herpes simplex virus 1 (hsv-1) and human cytomegalovirus (hcmv), and to lesser extent in herpes simplex virus 2 (hsv-2), varicella zoster virus (vzv) and human herpesvirus 6 (hhv ...201627694307
herpes simplex virus particles interact with chemokines and enhance cell migration.herpes simplex virus type 1 and type 2 (hsv-1 and hsv-2, respectively) are among the most prevalent human pathogens, causing a variety of diseases. hsv modulation of the chemokine network remains poorly understood. we have previously identified secreted glycoprotein g (sgg) as the first viral chemokine-binding protein that enhances chemokine function as a novel viral immunomodulatory mechanism. however, gg is also present at the viral envelope and its role in the virus particle remains unknown. ...201627692045
hsv-2 enhances zikv infection of the placenta and induces apoptosis in first-trimester trophoblast cells.zika virus (zikv) has gained public concern for its association with microcephaly in infants born to zikv-infected mothers. to reach the fetus the virus must overcome the defense mechanisms provided by trophoblast cells. additionally, in the first trimester, the integrity of the placenta is critical for fetal protection as damage to differentiating trophoblast can affect placental formation and function. we sought to investigate the effect of zikv infection on trophoblast cells and the factors t ...201627613665
database on natural polymorphisms and resistance-related non-synonymous mutations in thymidine kinase and dna polymerase genes of herpes simplex virus types 1 and 2.the use of genotypic resistance testing of herpes simplex virus types 1 and 2 (hsv-1 and hsv-2) is increasing because the rapid availability of results significantly improves the treatment of severe infections, especially in immunocompromised patients. however, an essential precondition is a broad knowledge of natural polymorphisms and resistance-associated mutations in the thymidine kinase (tk) and dna polymerase (pol) genes, of which the dna polymerase (pol) enzyme is targeted by the highly ef ...201626433780
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