Abstract:
:During all stages of infection, herpes simplex virus 1 (HSV-1) expresses viral microRNAs (miRNAs). There are at least 20 confirmed HSV-1 miRNAs, yet the roles of individual miRNAs in the context of viral infection remain largely uncharacterized. We constructed a recombinant virus lacking the sequences for miR-H1-5p and miR-H6-3p (17dmiR-H1/H6). The seed sequences for these miRNAs are antisense to each other and are transcribed from divergent noncoding RNAs in the latency-associated transcript (LAT) promoter region. Comparing phenotypes exhibited by the recombinant virus lacking these miRNAs to the wild type (17syn+), we found that during acute infection in cell culture, 17dmiR-H1/H6 exhibited a modest increase in viral yields. Analysis of pathogenesis in the mouse following footpad infection revealed a slight increase in virulence for 17dmiR-H1/H6 but no significant difference in the establishment or maintenance of latency. Strikingly, explant of latently infected dorsal root ganglia revealed a decreased and delayed reactivation phenotype. Further, 17dmiR-H1/H6 was severely impaired in epinephrine-induced reactivation in the rabbit ocular model. Finally, we demonstrated that deletion of miR-H1/H6 increased the accumulation of the LAT as well as several of the LAT region miRNAs. These results suggest that miR-H1/H6 plays an important role in facilitating efficient reactivation from latency.IMPORTANCE While HSV antivirals reduce the severity and duration of clinical disease in some individuals, there is no vaccine or cure. Therefore, understanding the mechanisms regulating latency and reactivation as a potential to elucidate targets for better therapeutics is important. There are at least 20 confirmed HSV-1 miRNAs, yet the roles of individual miRNAs in the context of viral infection remain largely uncharacterized. The present study focuses on two of the miRNAs (miR-H1/H6) that are encoded within the latency-associated transcript (LAT) region, a portion of the genome that has been associated with efficient reactivation. Here, we demonstrate that the deletion of the seed sequences of these miRNAs results in a severe reduction in reactivation of HSV-1 in the mouse and rabbit models. These results suggest a linkage between these miRNAs and reactivation.
journal_name
J Viroljournal_title
Journal of virologyauthors
Barrozo ER,Nakayama S,Singh P,Vanni EAH,Arvin AM,Neumann DM,Bloom DCdoi
10.1128/JVI.00639-20subject
Has Abstractpub_date
2020-07-16 00:00:00issue
15eissn
0022-538Xissn
1098-5514pii
JVI.00639-20journal_volume
94pub_type
杂志文章abstract::This study on Tomato bushy stunt virus identified and defined three previously unknown regulatory sequences involved in RNA accumulation that are located within the 3'-proximal nested movement protein genes p22 and p19. The first is a 16-nucleotide (nt) element termed III-A that is positioned at the very 3' end of p22...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.24.12747-12757.2002
更新日期:2002-12-01 00:00:00
abstract::Previous analyses using in situ hybridization alone or together with PCR have yielded conflicting results regarding the cell type in which latent varicella-zoster virus (VZV) resides. We separated human trigeminal ganglia (TG) into neuronal and nonneuronal fractions, followed by primary and nested PCR to quantitate VZ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.10.8571-8577.1999
更新日期:1999-10-01 00:00:00
abstract:UNLABELLED:Aminoquinolines and piperazines, linked or not, have been used successfully to treat malaria, and some molecules of this family also exhibit antiviral properties. Here we tested several derivatives of 4-aminoquinolines and piperazines for their activity against hepatitis C virus (HCV). We screened 11 molecul...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00404-16
更新日期:2016-09-12 00:00:00
abstract::Previous recombinant Epstein-Barr virus molecular genetic experiments with specifically mutated LMP1 genes indicate that LMP1 is essential for primary B-lymphocyte growth transformation and that the amino-terminal cytoplasmic and first transmembrane domains are together an important mediator of transformation. EBV rec...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.7.4369-4376.1994
更新日期:1994-07-01 00:00:00
abstract::The antigenic binding sites of two monoclonal antibodies are located in the COOH-terminal region (clone 412) and probably in an internal region (clone 7) of simian virus 40 large T antigen. A third monoclonal antibody (clone 122), which has been shown to bind nonviral T antigen, does not react with HeLa cells infected...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.37.1.478-482.1981
更新日期:1981-01-01 00:00:00
abstract::We have previously demonstrated that two mouse cell lines that are poorly infectible by reovirus become highly susceptible upon transfection with the gene encoding the epidermal growth factor receptor (EGFR) (J. E. Strong, D. Tang, and P. W. K. Lee, Virology 197:405-411, 1993). This enhancement of infection efficiency...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.1.612-616.1996
更新日期:1996-01-01 00:00:00
abstract::The family Bunyaviridae is the most diversified family of RNA viruses. We describe a novel prototypic bunyavirus, tentatively named Gouléako virus, isolated from various mosquito species trapped in Côte d'Ivoire. The S segment comprised 1,087 nucleotides (nt), the M segment 3,188 nt, and the L segment 6,358 nt, consti...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00230-11
更新日期:2011-09-01 00:00:00
abstract:UNLABELLED:Varicella-zoster virus (VZV) is an alphaherpesvirus that causes varicella and herpes zoster. Membrane fusion is essential for VZV entry and the distinctive syncytium formation in VZV-infected skin and neuronal tissue. Herpesvirus fusion is mediated by a complex of glycoproteins gB and gH-gL, which are necess...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00792-16
更新日期:2016-07-27 00:00:00
abstract::Transcriptionally active replication complexes bound to smooth membrane vesicles were isolated from poliovirus-infected cells. In electron microscopic, negatively stained preparations, the replication complex appeared as an irregularly shaped, oblong structure attached to several virus-induced vesicles of a rosettelik...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.3.1156-1163.1990
更新日期:1990-03-01 00:00:00
abstract::Glycoprotein H (gH) is conserved among all herpesviruses and is essential for virus entry and cell fusion along with gL, gB, and, in most alphaherpesviruses, gD. Within the gH/gL heterodimer, it is thought that gH accounts for the fusion function and gL acts as a chaperone for the folding and transport of gH. Here, we...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00097-07
更新日期:2007-05-01 00:00:00
abstract::A window of opportunity for immune responses to extinguish human immunodeficiency virus type 1 (HIV-1) exists from the moment of transmission through establishment of the latent pool of HIV-1-infected cells. A critical time to study the initial immune responses to the transmitted/founder virus is the eclipse phase of ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01708-08
更新日期:2008-12-01 00:00:00
abstract::The RNA elements that are required for replication of defective interfering (DI) RNA of the JHM strain of mouse hepatitis virus (MHV) consist of three discontinuous genomic regions: about 0.46 to 0.47 kb from both terminal sequences and an internal 58-nucleotide (nt)-long sequence (58-nt region) present at about 0.9 k...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.10.7926-7933.1998
更新日期:1998-10-01 00:00:00
abstract::Ribosomes from ghost-treated Escherichia coli can form in vitro initiation complexes but cannot translate added template RNA because of a defect in the 30S subunit; 16S rRNA is degraded. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.14.5.1310-1313.1974
更新日期:1974-11-01 00:00:00
abstract::The expression of a human immunodeficiency virus (HIV) type 1 provirus (F12-HIV) cloned from a nonproducer, chronically infected CD4 down-regulated Hut-78 cell clone (F12) does not lead to the formation of viral particles and, upon transfection in HeLa CD4+ cells, confers resistance to HIV superinfection without affec...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.11.6618-6626.1995
更新日期:1995-11-01 00:00:00
abstract::Alfalfa mosaic virus (AMV) and ilarvirus RNAs are infectious only in the presence of the viral coat protein; therefore, an understanding of coat protein's function is important for defining viral replication mechanisms. Based on in vitro replication experiments, the conformational switch model states that AMV coat pro...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.9.5752-5761.2005
更新日期:2005-05-01 00:00:00
abstract::The synthesis of Sendai virus RNA species was examined after UV irradiation of cells late in infection. Compared with the inactivation of 50S genomic RNA synthesis, the synthesis of the group of mRNA species that sediments at 18S was inactivated at an average rate consistent with a process of sequential transcription ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.21.3.863-871.1977
更新日期:1977-03-01 00:00:00
abstract::The synthesis of closed circular simian virus 40 (SV40) deoxyribonucleic acid (DNA) containing sequences homologous to host cell DNA depends upon the conditions under which the cells are infected. When BS-C-1 monkey cells were infected with non-plaque-purified virus at low multiplicity of infection [MOI, 0.032 plaque-...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.9.2.309-316.1972
更新日期:1972-02-01 00:00:00
abstract::The herpes simplex virus type 1 (HSV-1) UL25 gene contains a 580-amino-acid open reading frame that codes for an essential protein. Previous studies have shown that the UL25 gene product is a virion component (M. A. Ali et al., Virology 216:278-283, 1996) involved in virus penetration and capsid assembly (C. Addison e...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.2.1060-1070.1998
更新日期:1998-02-01 00:00:00
abstract::The DNA product of the endogenously instructed RNA-dependent DNA polymerase reaction of murine sarcoma virus continued to be synthesized for as long as 64 h in the presence of 0.008% Triton X-100. Higher detergent concentrations and actinomycin D inhibited DNA product synthesis. The DNA product from long-term polymera...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.12.5.1049-1064.1973
更新日期:1973-11-01 00:00:00
abstract::Recombinant strains of replication-competent rhesus monkey rhadinovirus (RRV) were constructed in which strong promoter/enhancer elements were used to drive expression of simian immunodeficiency virus (SIV) Env or Gag or a Rev-Tat-Nef fusion protein. Cultured rhesus monkey fibroblasts infected with each recombinant st...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00865-11
更新日期:2011-12-01 00:00:00
abstract:UNLABELLED:Despite the nutritional and health benefits of breast milk, breast milk can serve as a vector for mother-to-child HIV transmission. Most HIV-infected infants acquire HIV through breastfeeding. Paradoxically, most infants breastfed by HIV-positive women do not become infected. This is potentially attributed t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01702-15
更新日期:2015-11-01 00:00:00
abstract::Scrapie and Creutzfeldt-Jakob disease are transmissible, degenerative neurological diseases caused by prions. Considerable evidence argues that prions contain protease-resistant sialoglycoproteins, designated PrPSc, encoded by a cellular gene. The prion protein (PrP) gene also encodes a normal cellular protein designa...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.5.1558-1564.1988
更新日期:1988-05-01 00:00:00
abstract::We have found that the replicative helicase E1 of bovine papillomavirus type 1 (BPV-1) interacts with a key cell cycle regulator of S phase, the cyclin E-Cdk2 kinase. The E1 helicase, which interacts with cyclin E and not with Cdk2, presents the highest affinity for catalytically active kinase complexes. In addition, ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.9.7255-7262.1998
更新日期:1998-09-01 00:00:00
abstract::We have detected a mouse mammary tumor virus (MMTV)-specific 1.7-kilobase (kb) polyadenylated RNA in mammary glands of several mouse strains. In BALB/c mice, it is the only MMTV-specific RNA species present. C3H and GR mammary glands and tumors contain, in addition, 3.8- and 7.8-kb MMTV RNAs. Nuclease S1 analysis was ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.46.2.362-370.1983
更新日期:1983-05-01 00:00:00
abstract::Prior immunity to influenza A virus (IAV) in mice changes the outcome to a subsequent lymphocytic choriomeningitis virus (LCMV) infection and can result in severe lung pathology, similar to that observed in patients that died of the 1918 H1N1 pandemic. This pathology is induced by IAV-specific memory CD8(+) T cells cr...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00936-13
更新日期:2013-12-01 00:00:00
abstract::A region of the herpesvirus saimiri genome encoding an mRNA with two open reading frames (ORFs) has been identified to be essential for transformation of T cells. Deletion of either ORF resulted in the loss of transforming ability. ORF-1 has been shown to code for a collagen-like oncoprotein. This study shows for the ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.7.4495-4499.1995
更新日期:1995-07-01 00:00:00
abstract::Herpes simplex virus (HSV) fusion with cells requires the gD, gB, and gH/gL glycoprotein quartet. gD serves as a receptor binding glycoprotein. gB and gH/gL execute fusion in an as-yet-unclear manner. To better understand the role of gH/gL in HSV entry, we produced a soluble version of gH/gL carrying a One-STrEP tag (...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02502-09
更新日期:2010-04-01 00:00:00
abstract::We analyzed the CD4+ T-lymphocyte responses to dengue, West Nile, and yellow fever viruses 4 months after immunization of a volunteer with an experimental live-attenuated dengue virus type 1 vaccine (DEN-1 45AZ5). We examined bulk culture proliferation to noninfectious antigens, determined the precursor frequency of s...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.10.5962-5967.1993
更新日期:1993-10-01 00:00:00
abstract::The HXLF (HindIII-X left reading frame) gene family is a group of five genes that share one or two regions of homology and are arranged in tandem within the short unique component of the human cytomegalovirus genome (K. Weston and B.G. Barrell, J. Mol. Biol. 192:177-208, 1986). These genes were cloned into an SP6 expr...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.6.1956-1962.1988
更新日期:1988-06-01 00:00:00
abstract::A human cytomegalovirus (CMV) UL54 pol exonuclease domain II mutation, D413A, found in a clinical specimen, conferred ganciclovir (GCV) and cidofovir resistance but not foscarnet resistance when incorporated into laboratory strain T2294. After several passages without drug, mutation was observed in five of eight plaqu...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01787-07
更新日期:2008-01-01 00:00:00