Abstract:
:Coinfection with HIV-1 and Kaposi's sarcoma-associated herpesvirus (KSHV) often leads to AIDS-related malignancies, including Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL). The interaction between HIV and KSHV plays a pivotal role in the progression of these malignancies. We have previously demonstrated that, by upregulating miR-942-5p, HIV-1 viral protein R (Vpr) inhibits KSHV lytic replication by targeting IκBα to activate the NF-κB signaling (Q. Yan, C. Shen, J. Qin, W. Li, M. Hu, H. Lu, D. Qin, J. Zhu, S. J. Gao, C. Lu, J Virol 90:8739-8753, 2016). Here, we show that Vpr inactivates Notch signaling, resulting in inhibition of KSHV lytic replication and induction of pro-proliferative and -survival cytokines, including interleukin-2 (IL-2), TIMP-1, IGF-1, and NT-4. Mechanistically, Vpr upregulates miR-711, which directly targets the Notch1 3' untranslated region. Suppression of miR-711 relieved Notch1 and reduced Vpr inhibition of KSHV lytic replication and Vpr induction of pro-proliferation and -survival cytokines, while overexpression of miR-711 exhibited the opposite effect. Finally, overexpression of Notch1 reduced Vpr induction of NF-κB activity by promoting IκBα promoter activity. Our novel findings reveal that by upregulating miR-711 to target Notch1, Vpr silences Notch signaling to activate the NF-κB pathway by reducing IκBα expression, leading to inhibition of KSHV lytic replication and induction of pro-proliferation and -survival cytokines. Therefore, the miR-711/Notch/NF-κB axis is important in the pathogenesis of AIDS-related malignancies and could be an attractive therapeutic target.IMPORTANCE HIV-1 infection significantly increases the risk of KS and PEL in KSHV-infected individuals. Our previous study has shown that HIV-1 Vpr regulates the KSHV life cycle by targeting IκBα to activate NF-κB signaling through upregulating cellular miR-942-5p. In this study, we have further found that Vpr inactivates Notch signaling to promote KSHV latency and production of pro-proliferation and -survival cytokines. Another Vpr-upregulated cellular microRNA, miR-711, participates in this process by directly targeting Notch1. As a result, Notch1 upregulation of the IκBα promoter activity is attenuated, resulting in reduced levels of IκBα transcript and protein. Overall, these results illustrate an alternative mechanism of HIV-1 Vpr regulation of KSHV latency and aberrant cytokines through the miR-711/Notch/NF-κB axis. Our novel findings further demonstrate the role of an HIV-1-secreted regulatory protein in the KSHV life cycle and KSHV-related malignancies.
journal_name
J Viroljournal_title
Journal of virologyauthors
Yan Q,Zhao R,Shen C,Wang F,Li W,Gao SJ,Lu Cdoi
10.1128/JVI.00580-18subject
Has Abstractpub_date
2018-08-29 00:00:00issue
18eissn
0022-538Xissn
1098-5514pii
JVI.00580-18journal_volume
92pub_type
杂志文章abstract::Adenovirus (Ad) entry into cells is initiated by the binding of the fiber knob to a cell surface receptor. The coxsackie- and adenovirus receptor (CAR) functions as the attachment receptor for many, but not all, Ad serotypes. Ad type 37 (Ad37), a subgroup D virus that causes keratoconjunctivitis in humans, does not in...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.11.5375-5380.2001
更新日期:2001-06-01 00:00:00
abstract::The murine monoclonal antibody (MAb) 5A8, which is reactive with domain 2 of CD4, blocks human immunodeficiency virus type 1 (HIV-1) infection and syncytium formation of CD4+ cells (L. C. Burkly, D. Olson, R. Shapiro, G. Winkler, J. J. Rosa, D. W. Thomas, C. Williams, and P. Chisholm, J. Immunol., in press). Here we s...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.8.4784-4793.1992
更新日期:1992-08-01 00:00:00
abstract::To investigate E7-dependent biochemical changes which are involved in cellular transformation, we analyzed the influence of human papillomavirus type 16 (HPV-16) E7 on the expression of cell cycle regulatory proteins. Expression of E7 in established rodent fibroblasts (NIH 3T3), which was shown to be sufficient for tr...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.10.6389-6399.1995
更新日期:1995-10-01 00:00:00
abstract::Infection of domestic rabbits with cottontail rabbit papillomavirus (CRPV) causes local papillomas which progress to carcinomas in more than 80% of cases. This animal model system therefore allows the identification of molecular mechanisms required for the induction and progression of epithelial tumors. The viral E2 p...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.22.11209-11215.2002
更新日期:2002-11-01 00:00:00
abstract::African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal viral disease of domestic pigs that has significant economic consequences for the swine industry. The control of African swine fever (ASF) has been hampered by the unavailability of vaccines. Successful experimental vaccines hav...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01760-16
更新日期:2016-12-16 00:00:00
abstract::The major immediate-early (MIE) gene of human cytomegalovirus (HCMV) produces multiple mRNAs through differential splicing and polyadenylation. Reverse transcriptase PCR was used to characterize transcripts from exons 1, 2, 3, and 4 (immediate-early 1 [IE1]). The expected IE72 and IE19 mRNAs were detected, as well as ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.15.8191-8200.2004
更新日期:2004-08-01 00:00:00
abstract::Hepatitis A virus (HAV) 3C proteinase expressed in Escherichia coli was purified to homogeneity, and its cleavage specificity towards various parts of the viral polyprotein was analyzed. Intermolecular cleavage of the P2-P3 domain of the HAV polyprotein gave rise to proteins 2A, 2B, 2C, 3ABC, and 3D, suggesting that i...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.3.1727-1733.1995
更新日期:1995-03-01 00:00:00
abstract::The host cell receptor for Moloney murine leukemia virus was solubilized from murine L-cell membranes and characterized. In initial studies designed to identify a receptor-rich cell line, different mouse cells were screened for binding to Moloney gp70, the viral envelope glycoprotein which determines host cell-binding...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.58.3.900-908.1986
更新日期:1986-06-01 00:00:00
abstract::Polymorphic basic residues near the C terminus of the prion protein (PrP) in humans and sheep appear to protect against prion disease. In heterozygotes, inhibition of prion formation appears to be dominant negative and has been simulated in cultured cells persistently infected with scrapie prions. The results of nucle...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.9.4351-4360.2000
更新日期:2000-05-01 00:00:00
abstract::Herpes simplex virus type 1 (HSV-1) B capsids are composed of seven proteins, designated VP5, VP19C, 21, 22a, VP23, VP24, and VP26 in order of decreasing molecular weight. Three proteins (21, 22a, and VP24) are encoded by a single open reading frame (ORF), UL26, and include a protease whose structure and function have...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.9.5365-5374.1994
更新日期:1994-09-01 00:00:00
abstract::Chikungunya virus (CHIKV) is a mosquito-borne alphavirus responsible for chikungunya fever. Nonstructural protein 2 (nsP2), a multifunctional protein essential for viral replication, has an N-terminal helicase region (nsP2h), which as both nucleotide triphosphatase and RNA triphosphatase activities, as well as a C-ter...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01470-20
更新日期:2020-12-16 00:00:00
abstract::The Us11 protein of herpes simplex virus 1 (HSV-1) is an accessory factor with multiple functions. In virus-infected cells, it inhibits double-stranded RNA-dependent protein kinase (PKR), 2',5'-oligoadenylate synthetase, RIG-I, and MDA-5. However, its precise role is incompletely defined. By screening a human cDNA lib...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00402-18
更新日期:2018-06-29 00:00:00
abstract::Tryptic digests of four polypeptides found in Kunjin virus-infected Vero cells, NV5, NV4, V3, and NV3, were compared by peptide mapping. The polypeptides to be analyzed were labeled with radioactive methionine and separated by electrophoresis through polyacrylamide gels containing sodium dodecyl sulfate. Because infec...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.24.2.651-661.1977
更新日期:1977-11-01 00:00:00
abstract::The replication of the simian herpesvirus SA8 in Vero cells was examined. The time course of replication of the simian herpesvirus SA8 was found to be similar to that of the herpes simplex viruses. Infectious progeny virions were first detectable by 6 h postinfection and were readily released into the extracellular fl...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.50.2.316-324.1984
更新日期:1984-05-01 00:00:00
abstract::Previous analyses have demonstrated that adenovirus DNA is packaged into virions in vivo in a polar, left-to-right fashion. The packaging of viral DNA is dependent on cis-acting elements at the left end of the genome. In this report, we describe a genetic analysis of the sequences that are required for efficient packa...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.5.2047-2056.1990
更新日期:1990-05-01 00:00:00
abstract::To examine the pathway of the coreceptor switching of CCR5-using (R5) virus to CXCR4-using (X4) virus in simian-human immunodeficiency virus SHIV(SF162P3N)-infected rhesus macaque BR24, analysis was performed on variants present at 20 weeks postinfection, the time when the signature gp120 V3 loop sequence of the X4 sw...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00570-08
更新日期:2008-07-01 00:00:00
abstract::We analyzed xenotropic murine leukemia virus-related virus (XMRV) integration site sequences previously identified from human prostate tissues for single-nucleotide polymorphisms (SNPs) to discriminate between patient and potential cell line sources of the proviruses. The SNPs of two integration sites were identical t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.05624-11
更新日期:2011-12-01 00:00:00
abstract::Sequence analysis of the Lymantria dispar multicapsid nucleopolyhedrovirus (LdMNPV) genome identified an open reading frame (ORF) encoding a 548-amino-acid (62-kDa) protein that showed 35% amino acid sequence identity with vaccinia virus ATP-dependent DNA ligase. Ligase homologs have not been reported from other bacul...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.11.9142-9149.1998
更新日期:1998-11-01 00:00:00
abstract::The 11th influenza A virus gene product is an 87-amino-acid protein provisionally named PB1-F2 (because it is encoded by an open reading frame overlapping the PB1 open reading frame). A significant fraction of PB1-F2 localizes to the inner mitochondrial membrane in influenza A virus-infected cells. PB1-F2 appears to e...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.13.7214-7224.2003
更新日期:2003-07-01 00:00:00
abstract::Cell fractionation and protein electrophoresis were used to study the intracellular sites of synthesis and intermediate structures in the assembly of the virion proteins of vesicular stomatitis virus. Each of the three major virion proteins assembled into virions through a separable pathway. The nucleocapsid (N) prote...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.21.3.1128-1139.1977
更新日期:1977-03-01 00:00:00
abstract::Echovirus 1 (EV1) is a human pathogen which belongs to the Picornaviridae family of RNA viruses. We have analyzed the early events of infection after EV1 binding to its receptor alpha 2 beta 1 integrin and elucidated the route by which EV1 gains access to the host cell. EV1 binding onto the cell surface and subsequent...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.4.1856-1865.2002
更新日期:2002-02-01 00:00:00
abstract::Type C RNA viruses initially isolated from a lymphosarcoma of a gibbon ape and from a fibrosarcoma of a woolly monkey are very closely related immunologically. However, recent studies have shown that these viruses are distinguishable in a radioimmunoassay for the 12,000-molecular-weight polypeptide (p12) of the woolly...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.15.1.115-120.1975
更新日期:1975-01-01 00:00:00
abstract::The phenomenon whereby the host immune system responds to only a few of the many possible epitopes in a foreign protein is termed immunodominance. Immunodominance occurs not only during microbial infection but also following vaccination, and clarification of the underlying mechanism may permit the rational design of v...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.9.4251-4259.2002
更新日期:2002-05-01 00:00:00
abstract::A protocol was designed to measure the forward mutation rate over an entire gene replicated as part of a Moloney murine leukemia virus-based vector. For these studies, the herpes simplex virus thymidine kinase (tk) gene under the control of the spleen necrosis virus U3 promoter was used as target sequence since it all...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.11.6357-6364.1993
更新日期:1993-11-01 00:00:00
abstract::The HIV-1 spike is composed of three protomeric units, each containing a peripheral gp120 and a transmembrane gp41 subunit. Binding to the CD4 and the chemokine receptors triggers them to mediate virus entry into cells by membrane fusion. The spikes also represent the major target for neutralizing antibodies (Abs) aga...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00530-13
更新日期:2013-06-01 00:00:00
abstract::The nature of the lesions involved in producing the fusiform phenotype of three mutants (WO101, WO201, and tsST529) of the Schmidt-Ruppin A strain of Rous sarcoma virus (RSV) was determined by molecular cloning and DNA sequencing. WO101 and WO201 contained an in-frame deletion of the v-src region coding for amino acid...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.6.1893-1900.1987
更新日期:1987-06-01 00:00:00
abstract::We report several biological activities of a synthetic peptide whose sequence contains the highly conserved region of feline leukemia virus transmembrane protein (TM) synthetically linked to another short TM-derived sequence particularly rich in polar positive residues. This 29-amino-acid peptide blocked [3H]thymidine...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.4.1429-1436.1990
更新日期:1990-04-01 00:00:00
abstract::The susceptibility to tumors induced by raf and raf/myc retroviruses was investigated in BALB/c, C57BL/6, (BALB/c x C57BL/6)F1 and (BALB/c x C57BL/6) backcross mice. Newborn mice were susceptible to neoplasms generated by both viruses, but resistance to raf-induced leukemia developed rapidly in all mice as they mature...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.5.2411-2414.1989
更新日期:1989-05-01 00:00:00
abstract::The cloned murine cytolytic T-lymphocyte line IE1-IL and several sublines detect a murine cytomegalovirus immediate-early (IE) membrane determinant in conjunction with Ld class I major histocompatibility glycoprotein. The lines retained cytolytic activity, strict antigen specificity, and self-restriction even when ada...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.60.3.1125-1129.1986
更新日期:1986-12-01 00:00:00
abstract::Recent findings suggest that most sexual transmission of human immunodeficiency virus type 1 (HIV-1) occurs during the acute phase of infection when viral replication is most intense. Here, we show that vaccine-elicited cellular immune responses can significantly reduce simian immunodeficiency virus levels in the seme...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01202-09
更新日期:2009-10-01 00:00:00