Abstract:
:Persistent infection with oncogenic human papillomaviruses (HPVs) causes cervical cancer, accompanied by the accumulation of somatic mutations into the host genome. There are concomitant genetic changes in the HPV genome during viral infection; however, their relevance to cervical carcinogenesis is poorly understood. Here, we explored within-host genetic diversity of HPV by performing deep-sequencing analyses of viral whole-genome sequences in clinical specimens. The whole genomes of HPV types 16, 52, and 58 were amplified by type-specific PCR from total cellular DNA of cervical exfoliated cells collected from patients with cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC) and were deep sequenced. After constructing a reference viral genome sequence for each specimen, nucleotide positions showing changes with >0.5% frequencies compared to the reference sequence were determined for individual samples. In total, 1,052 positions of nucleotide variations were detected in HPV genomes from 151 samples (CIN1, n = 56; CIN2/3, n = 68; ICC, n = 27), with various numbers per sample. Overall, C-to-T and C-to-A substitutions were the dominant changes observed across all histological grades. While C-to-T transitions were predominantly detected in CIN1, their prevalence was decreased in CIN2/3 and fell below that of C-to-A transversions in ICC. Analysis of the trinucleotide context encompassing substituted bases revealed that TpCpN, a preferred target sequence for cellular APOBEC cytosine deaminases, was a primary site for C-to-T substitutions in the HPV genome. These results strongly imply that the APOBEC proteins are drivers of HPV genome mutation, particularly in CIN1 lesions.IMPORTANCE HPVs exhibit surprisingly high levels of genetic diversity, including a large repertoire of minor genomic variants in each viral genotype. Here, by conducting deep-sequencing analyses, we show for the first time a comprehensive snapshot of the within-host genetic diversity of high-risk HPVs during cervical carcinogenesis. Quasispecies harboring minor nucleotide variations in viral whole-genome sequences were extensively observed across different grades of CIN and cervical cancer. Among the within-host variations, C-to-T transitions, a characteristic change mediated by cellular APOBEC cytosine deaminases, were predominantly detected throughout the whole viral genome, most strikingly in low-grade CIN lesions. The results strongly suggest that within-host variations of the HPV genome are primarily generated through the interaction with host cell DNA-editing enzymes and that such within-host variability is an evolutionary source of the genetic diversity of HPVs.
journal_name
J Viroljournal_title
Journal of virologyauthors
Hirose Y,Onuki M,Tenjimbayashi Y,Mori S,Ishii Y,Takeuchi T,Tasaka N,Satoh T,Morisada T,Iwata T,Miyamoto S,Matsumoto K,Sekizawa A,Kukimoto Idoi
10.1128/JVI.00017-18subject
Has Abstractpub_date
2018-05-29 00:00:00issue
12eissn
0022-538Xissn
1098-5514pii
JVI.00017-18journal_volume
92pub_type
杂志文章abstract::Ultrastructure was correlated with growth kinetics of bdellophage VL-1 infecting host-dependent ("parasitic") Bdellovibrio bacteriovorus 109J in its Escherichia coli B host (the three-membered system), as well as in the host-independent ("saprophytic") derivative of the Bdellovibrio. Electron microscope observations s...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.12.6.1522-1533.1973
更新日期:1973-12-01 00:00:00
abstract::BALB/c mice treated with pristane and Abelson virus have been used as an animal model system for the rapid induction of plasmacytomas. Myelomonocytic tumors with helper Moloney murine leukemia virus clonally inserted into the c-myb locus were observed in about 10% of pristane-primed BALB/c mice infected with Abelson v...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.12.3721-3725.1987
更新日期:1987-12-01 00:00:00
abstract::A tumor line (58-2T) was established from a slowly growing tumor in a BALB/c mouse inoculated with M58-2 cells. The latter clonal cell line was isolated after bromodeoxyuridine treatment as a flat variant from nonproducer BALB/3T3 cells transformed by the Kirsten sarcoma virus. The 58-2T cells produced type C virus wi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.14.5.1262-1267.1974
更新日期:1974-11-01 00:00:00
abstract::Hepatitis B virus particles contain three related viral envelope proteins, the small, middle, and large S (surface) proteins. All three proteins contain the small S amino acid sequence at their carboxyl terminus. It is not clear which of these S proteins functions as the viral attachment protein, binding to a target c...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.5.1981-1988.1989
更新日期:1989-05-01 00:00:00
abstract::Small-t antigen of simian virus 40 renders CV-1 cells resistant to growth arrest induced by theophylline and other methylxanthines. Elevated levels of cyclic AMP are not involved in growth arrest of CV-1 cells by methylxanthines, and small-t antigen does not alter cyclic AMP levels dramatically after infection. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.54.3.876-878.1985
更新日期:1985-06-01 00:00:00
abstract::We previously reported that the expression of rotavirus phenotypes by reassortants was affected by recipient genetic background and proposed specific interactions between the outer capsid proteins VP4 and VP7 as the basis for the phenotypic effects (D. Chen, J. W. Burns, M. K. Estes, and R. F. Ramig, Proc. Natl. Acad....
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.1.432-439.1992
更新日期:1992-01-01 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) impacts multiple lineages of hematopoietic cells, including lymphocytes and macrophages, either by direct infection or indirectly by perturbations of cell networks, leading to generalized immune deficiency. We designed a study to discover, in primary human macrophages, senti...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.21.11477-11486.2004
更新日期:2004-11-01 00:00:00
abstract::Type I interferon (IFN-I) inhibits the replication of different viruses. However, the effect of IFN-I on the human T-lymphotropic virus type 1 (HTLV-1) viral cycle is controversial. Here, we investigated the consequences of IFN-α addition for different steps of HTLV-1 and HTLV-2 infection. We first show that alpha int...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02758-13
更新日期:2013-12-01 00:00:00
abstract::Simian immunodeficiency virus (SIV) infection of rhesus macaques has become an important surrogate model for evaluating HIV vaccine strategies. The extreme resistance to neutralizing antibody (NAb) of many commonly used strains, such as SIVmac251/239 and SIVsmE543-3, limits their potential relevance for evaluating the...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00923-12
更新日期:2012-08-01 00:00:00
abstract::To identify retroviral antigenic determinants recognized by CD4+ T helper cells during tumor rejection, we established four noncytolytic, helper-type, CD4+ T-cell clones by limiting dilution cultures of mixed lymphocyte-tumor cultures from mice immune to a Friend virus-induced tumor, FBL-3. Among these, three T helper...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.8.4533-4542.1993
更新日期:1993-08-01 00:00:00
abstract::By marker rescue with cloned herpes simplex virus 2 DNA fragments, we have mapped the temperature-sensitive mutations of a series of herpes simplex virus 2 mutants to a region of the herpes simplex virus 2 genome that lies within or near the coding sequences for the major DNA-binding protein, ICP8. In cells infected w...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.45.1.332-342.1983
更新日期:1983-01-01 00:00:00
abstract::We isolated and characterized two spontaneous, weakly leukemogenic mutants of Rauscher spleen focus-forming virus (R-SFFV) that contain mutations in nonoverlapping regions of the membrane envelope (env) glycoprotein gene. As reported previously (M. Ruta and D. Kabat, J. Virol. 35:844-853, 1980), the replication-defect...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.49.2.394-402.1984
更新日期:1984-02-01 00:00:00
abstract::The human papillomavirus (HPV) type 16 (HPV16) E6 protein can stimulate mechanistic target of rapamycin complex 1 (mTORC1) signaling and cap-dependent translation through activation of the PDK1 and mTORC2 kinases. Here we report that HPV18 E6 also enhances cap-dependent translation. The integrity of LXXLL and PDZ prot...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00487-12
更新日期:2012-07-01 00:00:00
abstract::Hepatitis B virus (HBV) DNA clones were propagated from 57 carriers with antibody to hepatitis B e antigen (HBeAg) and sequenced within nucleotides (nt) 1685 to 1926 including the core promoter (nt 1742 to 1849) and the pre-C region (nt 1814 to 1900). Mutations in the core promoter or those in the pre-C region, or bot...
journal_title:Journal of virology
pub_type: 临床试验,杂志文章
doi:10.1128/JVI.68.12.8102-8110.1994
更新日期:1994-12-01 00:00:00
abstract::Recently developed antiviral strategies based upon RNA interference (RNAi), which harnesses an innate cellular system for the targeted down-regulation of gene expression, appear highly promising and offer alternative approaches to conventional highly active antiretroviral therapy or efforts to develop an AIDS vaccine....
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.3.1645-1654.2005
更新日期:2005-02-01 00:00:00
abstract::The bovine herpesvirus 1 (BHV-1) UL49 gene encodes a viral tegument protein termed VP22. UL49 homologs are conserved among alphaherpesviruses. Interestingly, the BHV-1 VP22 deletion mutant virus is asymptomatic and avirulent in infected cattle but produces only a slight reduction in titer in vitro. Attenuation of the ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.75.17.8251-8258.2001
更新日期:2001-09-01 00:00:00
abstract::Equine infectious anemia virus (EIAV) provides a natural model system by which immunological control of lentivirus infections may be studied. To date, no detailed study addressing in parallel both the humoral and cellular immune responses induced in horses upon infection by EIAV has been conducted. Therefore, we initi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.5.3840-3852.1997
更新日期:1997-05-01 00:00:00
abstract::Restriction factors are intrinsic cellular defense proteins that have evolved to block microbial infections. Retroviruses such as HIV-1 are restricted by TRIM5 proteins, which recognize the viral capsid shell that surrounds, organizes, and protects the viral genome. TRIM5α uses a SPRY domain to bind capsids with low i...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01563-17
更新日期:2018-01-30 00:00:00
abstract::We have previously described a nonconditional mutant of avian sarcoma virus (SE21Q1b) which fails to package viral RNA (Gallis et al., Virology 94:146-161, 1979; Linial et al., Cell 15:1371-1381, 1978). Quail cells transformed by SE21Q1b contain normal amounts of intracellular viral mRNA's for src, env, and gag-pol an...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.36.2.450-456.1980
更新日期:1980-11-01 00:00:00
abstract::Dendritic cells (DCs) play a central role in instructing antiviral immune responses. DCs, however, can become targeted by different viruses themselves. We recently demonstrated that human DCs can be productively infected with echoviruses (EVs), but not coxsackie B viruses (CVBs), both of which are RNA viruses belongin...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02376-07
更新日期:2008-03-01 00:00:00
abstract::Theiler's virus-induced demyelinating disease results from a chronic infection in the white matter of the central nervous system and provides an excellent model for human multiple sclerosis. Like multiple sclerosis, there are genetic risk factors in disease development, including genes associated with the major histoc...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.2.686-690.1990
更新日期:1990-02-01 00:00:00
abstract::The Kresse strain of porcine parvovirus (PPV) was cloned into pUC19, and independent infectious clones were sequenced. The PPV Kresse and NADL-2 strains, which have different pathogenicities, shared an identical genomic organization and a high degree of sequence identity. Partial genomes (1.5 or 1.6 kb) of 15 field is...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.4.2508-2515.1996
更新日期:1996-04-01 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) requires that its genome be reverse transcribed into double-stranded DNA for productive infection of cells. This process requires not only reverse transcriptase but also the nucleocapsid protein (NC), which functions as a nucleic acid chaperone. Reverse transcription general...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00583-08
更新日期:2008-10-01 00:00:00
abstract:UNLABELLED:Human immunodeficiency virus type 1 (HIV-1) infection in the central nervous system (CNS) is characterized by replication in macrophages or brain microglia that express low levels of the CD4 receptor and is the cause of HIV-associated dementia and related cognitive and motor disorders that affect 20 to 30% o...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01237-14
更新日期:2014-08-01 00:00:00
abstract::Superinfection exclusion is the ability of an established viral infection to interfere with a second viral infection. Using West Nile virus (WNV) as a model, we show that replicating replicons in BHK-21 cells suppress subsequent WNV infection. The WNV replicon also suppresses superinfections of other flaviviruses but ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01205-09
更新日期:2009-11-01 00:00:00
abstract:UNLABELLED:The brown planthopper (BPH), Nilaparvata lugens (Hemiptera:Delphacidae), is one of the most destructive insect pests of rice crops in Asia. Nudivirus-like sequences were identified during the whole-genome sequencing of BPH. PCR examination showed that the virus sequences were present in all of the 22 BPH pop...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03166-13
更新日期:2014-05-01 00:00:00
abstract::An mRNA-ribonucleoprotein particle (mRNP) was found in vesicular stomatitis virus (VSV)-infected Chinese hamster ovary cells. The particle was present 3 and 4.5 h after infection but was barely discernible at 2 h. The mRNP (buoyant density, 1.56 g/cm3), which cosedimented with viral nucleocapsid in a sucrose density g...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.44.3.932-938.1982
更新日期:1982-12-01 00:00:00
abstract::Previously we have described a stepwise, energy-dependent pathway for human immunodeficiency virus type 1 (HIV-1) capsid assembly in a cell-free system. In this pathway, Gag polypeptides utilize the cellular factor HP68 and assemble into immature capsids by way of assembly intermediates that have defined biochemical c...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.78.4.1645-1656.2004
更新日期:2004-02-01 00:00:00
abstract::Although in vitro replication of the hepatitis C virus (HCV) JFH1 clone of genotype 2a (HCVcc) has been developed, a robust cell culture system for the 1a and 1b genotypes, which are the most prevalent viruses in the world and resistant to interferon therapy, has not yet been established. As a surrogate virus system, ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00608-07
更新日期:2007-08-01 00:00:00
abstract::The structure of recombinant virus-like particles of malabaricus grouper nervous necrosis virus (MGNNV), a fish nodavirus isolated from the grouper Epinephelus malabaricus, was determined by electron cryomicroscopy (cryoEM) and three-dimensional reconstruction at 23-A resolution. The cryoEM structure, sequence compari...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.12.6370-6375.2002
更新日期:2002-06-01 00:00:00