Abstract:
UNLABELLED:The APOBEC3 family of DNA cytosine deaminases has important roles in innate immunity and cancer. It is unclear how DNA tumor viruses regulate these enzymes and how these interactions, in turn, impact the integrity of both the viral and cellular genomes. Polyomavirus (PyVs) are small DNA pathogens that contain oncogenic potentials. In this study, we examined the effects of PyV infection on APOBEC3 expression and activity. We demonstrate that APOBEC3B is specifically upregulated by BK polyomavirus (BKPyV) infection in primary kidney cells and that the upregulated enzyme is active. We further show that the BKPyV large T antigen, as well as large T antigens from related polyomaviruses, is alone capable of upregulating APOBEC3B expression and activity. Furthermore, we assessed the impact of A3B on productive BKPyV infection and viral genome evolution. Although the specific knockdown of APOBEC3B has little short-term effect on productive BKPyV infection, our informatics analyses indicate that the preferred target sequences of APOBEC3B are depleted in BKPyV genomes and that this motif underrepresentation is enriched on the nontranscribed stand of the viral genome, which is also the lagging strand during viral DNA replication. Our results suggest that PyV infection upregulates APOBEC3B activity to influence virus sequence composition over longer evolutionary periods. These findings also imply that the increased activity of APOBEC3B may contribute to PyV-mediated tumorigenesis. IMPORTANCE:Polyomaviruses (PyVs) are a group of emerging pathogens that can cause severe diseases, including cancers in immunosuppressed individuals. Here we describe the finding that PyV infection specifically induces the innate immune DNA cytosine deaminase APOBEC3B. The induced APOBEC3B enzyme is fully functional and therefore may exert mutational effects on both viral and host cell DNA. We provide bioinformatic evidence that, consistent with this idea, BK polyomavirus genomes are depleted of APOBEC3B-preferred target motifs and enriched for the corresponding predicted reaction products. These data imply that the interplay between PyV infection and APOBEC proteins may have significant impact on both viral evolution and virus-induced tumorigenesis.
journal_name
J Viroljournal_title
Journal of virologyauthors
Verhalen B,Starrett GJ,Harris RS,Jiang Mdoi
10.1128/JVI.00771-16subject
Has Abstractpub_date
2016-06-24 00:00:00pages
6379-6386issue
14eissn
0022-538Xissn
1098-5514pii
JVI.00771-16journal_volume
90pub_type
杂志文章abstract::The phosphoprotein (P protein) of respiratory syncytial virus (RSV) is a key component of the viral RNA-dependent RNA polymerase complex. The protein is constitutively phosphorylated at the two clusters of serine residues (116, 117, and 119 [116/117/119] and 232 and 237 [232/237]). To examine the role of phosphorylati...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.21.10776-10784.2002
更新日期:2002-11-01 00:00:00
abstract::Herpes simplex virus virions contain one or more functions which mediate shutoff of host protein synthesis, disaggregation of host polyribosomes, and degradation of host mRNA. We studied aspects of the host shutoff mechanism by using herpes simplex virus type 1 mutants deficient in virion-induced shutoff of host prote...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.7.2198-2207.1987
更新日期:1987-07-01 00:00:00
abstract::Carcinogenic progression of a human papillomavirus (HPV)-infected cell is often associated with integration of the viral genome in a manner which results in the loss of expression of the viral regulatory protein E2. One function of E2 is the regulation of expression of the viral oncogenes, E6 and E7. Introduction of t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.12.7791-7799.1995
更新日期:1995-12-01 00:00:00
abstract::High-risk human papillomaviruses encode two oncogenes, E6 and E7, expressed in nearly all cervical cancers. Although E7 protein is best known for its ability to inactivate the retinoblastoma tumor suppressor protein, pRb, many other activities for E7 have been proposed in in vitro studies. Herein, we describe studies ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.17.11392-11402.2005
更新日期:2005-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.1.173-184.1990
更新日期:1990-01-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.11.6165-6172.1991
更新日期:1991-11-01 00:00:00
abstract::Closed circular unintegrated DNA of the SEATO strain of gibbon ape leukemia virus (GaLV-S) was isolated from canine thymus fibroblasts after cocultivation with chronically infected bat lung fibroblasts. Restriction endonuclease HindIII cleaves GaLV-S DNA once, thus allowing isolation and cloning of HindIII-digested un...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.44.1.269-275.1982
更新日期:1982-10-01 00:00:00
abstract::Rio Bravo virus (RBV) is a member of the family Flaviviridae, genus Flavivirus. It belongs to a group of viruses in the genus with no known vector. In this report, we analyze the complete genome of the prototype RBV, strain M64. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00331-12
更新日期:2012-04-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.52.2.591-597.1984
更新日期:1984-11-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/jvi.76.11.5612-5626.2002
更新日期:2002-06-01 00:00:00
abstract::The bovine papillomavirus type 1 (BPV-1) E7 oncoprotein is required for the full transformation activity of the virus. Although BPV-1 E7 by itself is not sufficient to induce cellular transformation, it enhances the abilities of the other BPV-1 oncogenes to induce anchorage independence. We have been exploring the mec...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00422-07
更新日期:2007-09-01 00:00:00
abstract::Epstein-Barr virus (EBV) latent membrane protein 2A (LMP2A) is widely expressed in EBV-infected cells within the infected human host and EBV-associated malignancies, suggesting that LMP2A is important for EBV latency, persistence, and EBV-associated tumorigenesis. Previously, we demonstrated that LMP2A provides an ant...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00537-07
更新日期:2007-09-01 00:00:00
abstract::A panel of murine monoclonal antibodies (MAbs) to the human immunodeficiency virus type 1 trans-activator tat protein were characterized. The anti-tat MAbs were mapped to the different domains of the tat protein by Western blot (immunoblot) and Pepscan analyses. One-half of the MAbs tested mapped to the amino-terminal...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.2.962-965.1990
更新日期:1990-02-01 00:00:00
abstract::The human immunodeficiency virus type 1 (HIV-1) accessory protein Vpu enhances virus particle release by counteracting a host factor that retains virions at the surfaces of infected cells. It was recently demonstrated that cellular protein BST-2/CD317/Tetherin restricts HIV-1 release in a Vpu-dependent manner. Calcium...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01786-09
更新日期:2009-12-01 00:00:00
abstract::Hepatitis C virus (HCV) enters cells via a pH- and clathrin-dependent endocytic pathway. Scavenger receptor BI (SR-BI) and CD81 are important entry factors for HCV internalization into target cells. The SR-BI gene gives rise to at least two mRNA splice variants, SR-BI and SR-BII, which differ in their C termini. SR-BI...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02356-06
更新日期:2007-04-01 00:00:00
abstract::Using gel shift assays, we found that the human immunodeficiency virus type 1 (HIV-1) Tat protein (Tat-1) bound both HIV-1 and HIV-2 TAR RNAs with similar high affinities. In contrast, the HIV-2 Tat protein (Tat-2) bound only TAR-2 RNA with high affinity. We conclude that the weak in vivo activity of Tat-2 on the HIV-...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.2.1110-1121.1993
更新日期:1993-02-01 00:00:00
abstract:UNLABELLED:The DNA damage response (DDR) that evolved to repair host cell DNA damage also recognizes viral DNA entering the nucleus during infections. Here, we investigated the modulation of DDR signaling during de novo infection of primary endothelial cells by Kaposi's sarcoma-associated herpesvirus (KSHV). Phosphoryl...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03126-13
更新日期:2014-03-01 00:00:00
abstract::Adenovirus infections cause significant morbidity and mortality in immunocompromised patients, yet little is known about the immune response to adenovirus infections. We established a system for the generation of a cytotoxic immune response to adenovirus in vitro. Cytotoxic T cells (CTLs) were derived from normal dono...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.10.6733-6740.1996
更新日期:1996-10-01 00:00:00
abstract:UNLABELLED:Nonhuman primates (NHPs) are a historically important source of zoonotic viruses and are a gold-standard model for research on many human pathogens. However, with the exception of simian immunodeficiency virus (SIV) (family Retroviridae), the blood-borne viruses harbored by these animals in the wild remain i...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00573-16
更新日期:2016-07-11 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.9.4338-4345.1990
更新日期:1990-09-01 00:00:00
abstract::Lysine-specific demethylase 1 (LSD1) targets cellular proteins, including histone H3, p53, E2F, and Dnmt1, and is involved in the regulation of gene expression, DNA replication, the cell cycle, and the DNA damage response. LSD1 catalyzes demethylation of histone H3K9 associated with herpes simplex virus 1 (HSV-1) imme...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00974-20
更新日期:2020-09-15 00:00:00
abstract::Studies on deoxyribonucleic acid purified from the granulosis virus of Trichoplusia ni have revealed the presence of a closed, double-stranded superhelix which sediments at 95S relative to relaxed circles (74S) and linear (60S) forms. Molecular weight estimates show that this insect virus deoxyribonucleic acid has a s...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.9.4.710-713.1972
更新日期:1972-04-01 00:00:00
abstract::Kilham rat virus (KRV) was grown in a rat nephroma cell line and was purified by two isopycnic centrifugations in cesium chloride. The virus contains single-stranded deoxyribonucleic acid (DNA) with a molecular weight of approximately 1.6 x 10(6). The DNA was extracted from the virion by both phenol extraction and by ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.7.6.830-835.1971
更新日期:1971-06-01 00:00:00
abstract::Synthesis of the proteins of rabies virus was studied in hamster cells infected with UV-irradiated virus. The UV target size of genes L, N, M1, and M2 was measured during primary transcription. Except for N, the target size of the remaining genes was considerably larger than that of their physical sizes. The data fit ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.28.2.518-523.1978
更新日期:1978-11-01 00:00:00
abstract::Rotavirus NSP5 is a nonstructural protein that localizes in cytoplasmic viroplasms of infected cells. NSP5 interacts with NSP2 and undergoes a complex posttranslational hyperphosphorylation, generating species with reduced polyacrylamide gel electrophoresis mobility. This process has been suggested to be due in part t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.7.3461-3470.2002
更新日期:2002-04-01 00:00:00
abstract::The identification of several simian immunodeficiency virus mac251 (SIV(mac251)) cytotoxic T-lymphocyte epitopes recognized by CD8(+) T cells of infected rhesus macaques carrying the Mamu-A*01 molecule and the use of peptide-major histocompatibility complex tetrameric complexes enable the study of the frequency, bread...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.23.11483-11495.2001
更新日期:2001-12-01 00:00:00
abstract::The genome of bacteriophage phi 6 contains three segments of double-stranded RNA. Procapsid structures whose formation was directed by cDNA copies of the large genomic segment are capable of packaging the three viral message sense RNAs in the presence of ATP. Addition of UTP, CTP, and GTP results in the synthesis of m...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.5.2611-2616.1992
更新日期:1992-05-01 00:00:00
abstract::The role of the 5' nontranslated region in the replication of hepatitis A virus (HAV) was studied by analyzing the translation and replication of chimeric RNAs containing the encephalomyocarditis virus (EMCV) internal ribosome entry segment (IRES) and various lengths (237, 151, or 98 nucleotides [nt]) of the 5'-termin...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.5.2861-2868.1996
更新日期:1996-05-01 00:00:00
abstract::The genome of hepatitis A virus (HAV) was reverse transcribed into cDNA and molecularly cloned. cDNA clones coding for the capsid protein VP1 that carries the major HAV antigen were cloned into the expression vector pUR290 and expressed in Escherichia coli. The recombinant fusion protein reacted in an immunoblot with ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.11.3645-3647.1987
更新日期:1987-11-01 00:00:00
abstract::In an attempt to generate broadly cross-reactive, neutralizing monoclonal antibodies (MAbs) to simian immunodeficiency virus (SIV), we compared two immunization protocols using different preparations of oligomeric SIV envelope (Env) glycoproteins. In the first protocol, mice were immunized with soluble gp140 (sgp140) ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.17.7922-7935.2000
更新日期:2000-09-01 00:00:00