Abstract:
:AIDS-related human cytomegalovirus retinitis remains the leading cause of blindness among untreated HIV/AIDS patients worldwide. To study mechanisms of this disease, we used a clinically relevant animal model of murine cytomegalovirus (MCMV) retinitis with retrovirus-induced murine AIDS (MAIDS) that mimics the progression of AIDS in humans. We found in this model that MCMV infection significantly stimulates ocular suppressor of cytokine signaling 1 (SOCS1) and SOCS3, host proteins which hinder immune-related signaling by cytokines, including antiviral type I and type II interferons. The present study demonstrates that in the absence of retinal disease, systemic MCMV infection of mice without MAIDS, but not in mice with MAIDS, leads to mild stimulation of splenic SOCS1 mRNA. In sharp contrast, when MCMV is directly inoculated into the eyes of retinitis-susceptible MAIDS mice, high levels of intraocular SOCS1 and SOCS3 mRNA and protein are produced which are associated with significant intraocular upregulation of gamma interferon (IFN-γ) and interleukin-6 (IL-6) mRNA expression. We also show that infiltrating macrophages, granulocytes, and resident retinal cells are sources of intraocular SOCS1 and SOCS3 protein production during development of MAIDS-related MCMV retinitis, and SOCS1 and SOCS3 mRNA transcripts are detected in retinal areas histologically characteristic of MCMV retinitis. Furthermore, SOCS1 and SOCS3 are found in both MCMV-infected cells and uninfected cells, suggesting that these SOCS proteins are stimulated via a bystander mechanism during MCMV retinitis. Taken together, our findings suggest a role for MCMV-related stimulation of SOCS1 and SOCS3 in the progression of retinal disease during ocular, but not systemic, MCMV infection.IMPORTANCE Cytomegalovirus infection frequently causes blindness in untreated HIV/AIDS patients. This virus manipulates host cells to dysregulate immune functions and drive disease. Here, we use an animal model of this disease to demonstrate that cytomegalovirus infection within eyes during retinitis causes massive upregulation of immunosuppressive host proteins called SOCS. As viral overexpression of SOCS proteins exacerbates infection with other viruses, they may also enhance cytomegalovirus infection. Alternatively, the immunosuppressive effect of SOCS proteins may be protective against immunopathology during cytomegalovirus retinitis, and in such a case SOCS mimetics or overexpression treatment strategies might be used to combat this disease. The results of this work therefore provide crucial basic knowledge that contributes to our understanding of the mechanisms of AIDS-related cytomegalovirus retinitis and, together with future studies, may contribute to the development of novel therapeutic targets that could improve the treatment or management of this sight-threatening disease.
journal_name
J Viroljournal_title
Journal of virologyauthors
Chien H,Alston CI,Dix RDdoi
10.1128/JVI.00526-18subject
Has Abstractpub_date
2018-08-29 00:00:00issue
18eissn
0022-538Xissn
1098-5514pii
JVI.00526-18journal_volume
92pub_type
杂志文章abstract::Eucaryotic, viral, and bacteriophage DNA polymerases of the alpha-like family share blocks of sequence similarity, the most conserved of which has been designated region I. Region I includes a YGDTDS motif that is almost invariant within the alpha-like family and that is similar to a motif conserved among RNA-directed...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.12.5883-5890.1990
更新日期:1990-12-01 00:00:00
abstract::Respiratory syncytial (RS) virus infects the epithelium of the respiratory tract. We examined the replication and maturation of RS virus in two polarized epithelial cell lines, Vero C1008 and MDCK. Electron microscopy of RS virus-infected Vero C1008 cells revealed the presence of pleomorphic viral particles budding ex...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.4.2667-2673.1995
更新日期:1995-04-01 00:00:00
abstract::Recent clinical trials examining 3'-azido-3'-deoxythymidine (AZT, zidovudine, or Retrovir) combined with L-2', 3'-dideoxy-3'-thiacytidine (3TC or lamivudine) have shown that combination therapy with these nucleoside analogs affords significant virological and clinical benefits. The addition of 3TC to AZT delays AZT re...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.6.5093-5098.1998
更新日期:1998-06-01 00:00:00
abstract::We performed live cell visualization assays to directly assess the interaction between competing adeno-associated virus (AAV) and herpes simplex virus type 1 (HSV-1) DNA replication. Our studies reveal the formation of separate AAV and HSV-1 replication compartments and the inhibition of HSV-1 replication compartment ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02476-06
更新日期:2007-05-01 00:00:00
abstract::Residual hepatitis B virus (HBV) DNA can be detected in serum and liver after apparent recovery from transient infection. However, it is not known if this residual HBV DNA represents ongoing viral replication and antigen expression. In the current study, ducks inoculated with duck hepatitis B virus (DHBV) were monitor...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.19.12242-12252.2005
更新日期:2005-10-01 00:00:00
abstract::We have purified the seven virus-specific RNAs which were previously shown to be induced in Sac(-) cells upon infection with mouse hepatitis virus strain A59 (W. J. M. Spaan, P. J. M. Rottier, M. C. Horzinek, and B. A. M. van der Zeijst, Virology 108:424-434, 1981). The individual RNAs, prepared by agarose gel electro...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.38.1.20-26.1981
更新日期:1981-04-01 00:00:00
abstract::We observed two patterns of chemokine expression in the lungs of mice infected with murine gammaherpesvirus 68: peaks of chemokine expression correlated with or occurred after the peak of viral gene expression. Chemokine expression remained elevated through 29 days postinfection. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.20.10518-10523.2002
更新日期:2002-10-01 00:00:00
abstract::H5N1 and H9N2 avian influenza virus subtypes top the World Health Organization's list for the greatest pandemic potential. Inactivated H5N1 vaccines induce limited immune responses and, in the case of live-attenuated influenza virus vaccines (LAIV), there are safety concerns regarding the possibility of reassortment b...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02490-12
更新日期:2013-05-01 00:00:00
abstract:UNLABELLED:Foreskin is the principal site of heterosexual HIV-1 infection in men. However, little is known about HIV-1-specific immune responses or inflammation in foreskin. To the best of our knowledge, no previous studies have assessed immune responses to candidate HIV-1 vaccines in foreskin. Using the rhesus monkey ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03771-13
更新日期:2014-04-01 00:00:00
abstract::BALB/c mice infected on the scarified cornea with herpes simplex virus type 1 strain 35 [HSV-1(35)] rarely developed ocular disease even at challenge doses as high as 10(7) PFU per eye. In contrast, HSV-1(RE) consistently induced stromal keratitis at an inoculum of 2 x 10(4) PFU. The goal of this study was to determin...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.5.2187-2192.1990
更新日期:1990-05-01 00:00:00
abstract::Endogenous viral elements derived from nonretroviral RNA viruses have been described in various animal genomes. Whether they have a biological function, such as host immune protection against related viruses, is a field of intense study. Here, we investigated the repertoire of endogenous flaviviral elements (EFVEs) in...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00571-17
更新日期:2017-07-12 00:00:00
abstract:UNLABELLED:Influenza virus hemagglutinin (HA) mediates virus entry by binding to cell surface receptors and fusing the viral and endosomal membranes following uptake by endocytosis. The acidic environment of endosomes triggers a large-scale conformational change in the transmembrane subunit of HA (HA2) involving a loop...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00939-15
更新日期:2015-10-01 00:00:00
abstract::The envelope protein of human immunodeficiency virus type 1 HIV-1 undergoes proteolytic cleavage in the Golgi complex to produce subunits designated gp120 and gp41, which remain noncovalently associated. While gp41 has a well-characterized oligomeric structure, the maintenance of gp41-independent gp120 intersubunit co...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.10.4448-4455.2000
更新日期:2000-05-01 00:00:00
abstract::The Friend or Moloney mink cell focus-forming (MCF) virus encodes a recombinant-type envelope glycoprotein, gp70, that is closely related to the membrane glycoprotein, gp55, of Friend spleen focus-forming virus (SFFV). We have shown previously that gp55 has the ability to activate cell growth by binding to the cellula...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.5.2408-2414.1991
更新日期:1991-05-01 00:00:00
abstract::The DA strain of Theiler's virus, a murine picornavirus, causes a persistent infection of glial cells of the white matter of the spinal cord, associated with chronic inflammation and primary demyelination. The GDVII strain causes an acute fatal grey matter encephalomyelitis. We characterized the target cells of GDVII ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.5.3197-3200.1995
更新日期:1995-05-01 00:00:00
abstract::To assess whether nitric oxide synthase 2 (NOS2) fulfills the criteria of an innate resistance locus against an acute viral infection, we inoculated genetically deficient NOS2-/- mice with virulent ectromelia virus (EV), the causative agent of mousepox. NOS2-/- mice proved highly susceptible to EV yet showed no diminu...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.9.7703-7706.1998
更新日期:1998-09-01 00:00:00
abstract::We have studied initiation and regulation of early transcription of simian virus (SV40) DNA in vitro by eucaryotic RNA polymerase II, using both a crude HeLa cell extract and a partially purified calf thymus polymerase supplemented with a HeLa cell S100 fraction. Analysis of initiation sites by primer-directed cDNA sy...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.41.2.449-461.1982
更新日期:1982-02-01 00:00:00
abstract::Regulatory T (T(R)) cells maintain tolerance to self-antigens and control immune responses to alloantigens after organ transplantation. Here, we show that CD4(+) CD25(+) human T(R) cells suppress virus-specific T-cell responses. Depletion of T(R) cells from peripheral blood mononuclear cells enhances T-cell responses ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.78.5.2454-2459.2004
更新日期:2004-03-01 00:00:00
abstract::Influenza A virus (IAV) is a highly transmissible respiratory pathogen and a major cause of morbidity and mortality around the world. Nucleoprotein (NP) is an abundant IAV protein essential for multiple steps of the viral life cycle. Our recent proteomic study of the IAV-host interaction network found that TRIM41 (tri...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00905-18
更新日期:2018-07-31 00:00:00
abstract::Two virus-specific species of newly synthesized DNA were isolated from rat fibroblast cell cultures infected with the Kilham rat virus (RV). These two DNA species were purified; their behavior on hydroxyapatite chromatography and their sedimentation coefficients in sucrose gradients were determined. One of the two spe...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.20.1.86-95.1976
更新日期:1976-10-01 00:00:00
abstract::The configuration of latent varicella-zoster virus (VZV) DNA was analyzed by PCR. Template DNA for both internal and terminal VZV primers was present in a 1:1 ratio in ganglionic DNA, compared with a 15:1 ratio in DNA extracted from VZV virions, indicating that the VZV genomic termini are adjacent in latently infected...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.12.8151-8154.1995
更新日期:1995-12-01 00:00:00
abstract::The virion RNA of Moloney murine leukemia virus (MuLV) has been translated in eukaryotic cell-free systems derived from mouse L- and human HeLa cells. In both systems at least three polypeptides, approximately 60,000, 70,000, and 180,000 in apparent molecular weight, were formed in response to the added 35S MuLV RNA. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.18.2.627-635.1976
更新日期:1976-05-01 00:00:00
abstract::Herpesviruses use a cascade of interactions with different cell surface molecules to gain entry into cells. In many cases, this involves binding to abundant glycosaminoglycans or integrins followed by interactions with more limited cell surface proteins, leading to fusion with cellular membranes. Human cytomegalovirus...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01623-08
更新日期:2008-12-01 00:00:00
abstract::The membrane-associated alphavirus RNA replication complex contains four virus-encoded subunits, the nonstructural proteins nsP1 to nsP4. Semliki Forest virus (SFV) nsP1 is hydrophobically modified by palmitoylation of cysteines 418 to 420. Here we show that Sindbis virus nsP1 is also palmitoylated on the same site (c...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.15.6725-6733.2000
更新日期:2000-08-01 00:00:00
abstract::The papillomavirus E2 protein is a critical viral regulatory protein with transcription, DNA replication, and genome maintenance functions. We have previously identified the cellular bromodomain protein Brd4 as a major E2-interacting protein and established that it participates in tethering bovine papillomavirus type ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00447-07
更新日期:2007-09-01 00:00:00
abstract::We have previously characterized five proteins induced by the presence of the E2 open reading frame (ORF) region of bovine papillomavirus type 1 (BPV-1) in C127 mouse fibroblasts (R. M. Levenson, U. G. Brinckmann, M. K. O'Banion, E. J. Androphy, J. T. Schiller, F. Tabatabai, L. P. Turek, K. Neary, M. T. Chin, T. R. Br...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.7.3481-3488.1991
更新日期:1991-07-01 00:00:00
abstract:UNLABELLED:Uracil DNA glycosylases (UNG) are highly conserved proteins that preserve DNA fidelity by catalyzing the removal of mutagenic uracils. All herpesviruses encode a viral UNG (vUNG), and yet the role of the vUNG in a pathogenic course of gammaherpesvirus infection is not known. First, we demonstrated that the v...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03111-14
更新日期:2015-03-01 00:00:00
abstract::Borna disease virus infection of neonatal rats results in a characteristic behavioral syndrome and apoptosis of subsets of neurons in the hippocampus and cerebellum (neonatal Borna disease [NBD]). The cellular mechanisms leading to neurodevelopmental damage in NBD have not been fully elucidated. Insights into this mod...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00836-06
更新日期:2006-09-01 00:00:00
abstract::Processing of dengue virus type 2 polyprotein precursor NS3-NS4A-NS4B-NS5 could be mediated by the catalytically active NS3 protease domain and NS2B in trans at the dibasic sites NS3-NS4A and NS4B-NS5. Subcellular localization of the unprocessed precursor NS3-NS4A-NS4B-NS5 showed that it was confined to a distinct sub...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.12.7549-7554.1992
更新日期:1992-12-01 00:00:00
abstract::Ebola virus (EBOV) infections result in aggressive hemorrhagic fever in humans, with fatality rates reaching 90% and with no licensed specific therapeutics to treat ill patients. Advances over the past 5 years have firmly established monoclonal antibody (MAb)-based products as the most promising therapeutics for treat...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01548-18
更新日期:2019-02-19 00:00:00