Genomes and Genes
gag gene products
Summary: Proteins coded by the retroviral gag gene. The products are usually synthesized as protein precursors or POLYPROTEINS, which are then cleaved by viral proteases to yield the final products. Many of the final products are associated with the nucleoprotein core of the virion. gag is short for group-specific antigen.
- Fisher R, Chung H, Zhai Q, Robinson H, Sundquist W, Hill C. Structural and biochemical studies of ALIX/AIP1 and its role in retrovirus budding. Cell. 2007;128:841-52 pubmed..ALIX therefore serves as a flexible, extended scaffold that connects retroviral Gag proteins to ESCRT-III and other cellular-budding machinery...
- Camus G, Segura Morales C, Molle D, Lopez Verges S, Begon Pescia C, Cazevieille C, et al. The clathrin adaptor complex AP-1 binds HIV-1 and MLV Gag and facilitates their budding. Mol Biol Cell. 2007;18:3193-203 pubmed..We propose that AP-1 promotes Gag release by transporting it to intracellular sites of active budding, and/or by facilitating its interactions with other cellular partners. ..
- De Rose R, Batten C, Smith M, Fernandez C, Peut V, Thomson S, et al. Comparative efficacy of subtype AE simian-human immunodeficiency virus priming and boosting vaccines in pigtail macaques. J Virol. 2007;81:292-300 pubmed..These studies suggest priming of T-cell immunity to prevent AIDS in humans is possible, but differences in the immunogenicity of various subtype vaccines and broad cross-subtype protection are substantial hurdles...
- Jouvenet N, Neil S, Bess C, Johnson M, Virgen C, Simon S, et al. Plasma membrane is the site of productive HIV-1 particle assembly. PLoS Biol. 2006;4:e435 pubmed..We conclude that HIV-1 assembly is initiated and completed at the PM, and not at endosomal membranes. ..
- Pereyra F, Addo M, Kaufmann D, Liu Y, Miura T, Rathod A, et al. Genetic and immunologic heterogeneity among persons who control HIV infection in the absence of therapy. J Infect Dis. 2008;197:563-71 pubmed publisher..Even low-level viremia among HIV controllers was associated with measurable T cell dysfunction, which has implications for current prophylactic vaccine strategies. ..
- Navis M, Schellens I, van Baarle D, Borghans J, van Swieten P, Miedema F, et al. Viral replication capacity as a correlate of HLA B57/B5801-associated nonprogressive HIV-1 infection. J Immunol. 2007;179:3133-43 pubmed
- Kiepiela P, Ngumbela K, Thobakgale C, Ramduth D, Honeyborne I, Moodley E, et al. CD8+ T-cell responses to different HIV proteins have discordant associations with viral load. Nat Med. 2007;13:46-53 pubmed..These population-based data, suggesting the existence of both effective immune responses and responses lacking demonstrable biological impact in chronic HIV infection, are of relevance to HIV vaccine design and evaluation. ..
- Saez Cirion A, Sinet M, Shin S, Urrutia A, Versmisse P, Lacabaratz C, et al. Heterogeneity in HIV suppression by CD8 T cells from HIV controllers: association with Gag-specific CD8 T cell responses. J Immunol. 2009;182:7828-37 pubmed publisher..These results, on the one hand, suggest the importance of Gag responses in the antiviral potency of CD8(+) T cells from HICs and, on the other hand, propose that other host mechanisms may contribute to restraining HIV infection in HICs. ..
- Brumme Z, John M, Carlson J, Brumme C, Chan D, Brockman M, et al. HLA-associated immune escape pathways in HIV-1 subtype B Gag, Pol and Nef proteins. PLoS ONE. 2009;4:e6687 pubmed publisher..These resources should facilitate research in HIV epitope discovery and host-pathogen co-evolution, and are relevant to the continued search for an effective CTL-based AIDS vaccine. ..
- Sacha J, Chung C, Rakasz E, Spencer S, Jonas A, Bean A, et al. Gag-specific CD8+ T lymphocytes recognize infected cells before AIDS-virus integration and viral protein expression. J Immunol. 2007;178:2746-54 pubmed..0017) in SIV-infected rhesus macaques. These results suggest that HIV vaccines should focus CD8(+) T cell responses on Gag. ..
- Loh L, Batten C, Petravic J, Davenport M, Kent S. In vivo fitness costs of different Gag CD8 T-cell escape mutant simian-human immunodeficiency viruses for macaques. J Virol. 2007;81:5418-22 pubmed..The fitness impact of these mutations is KP9 > AF9 > KW9. These data provide insights into the differential utility of CTL in controlling viremia...
- Bukrinskaya A. HIV-1 matrix protein: a mysterious regulator of the viral life cycle. Virus Res. 2007;124:1-11 pubmed..It is suggested that two MA fractions possess diverse functions and are involved in different stages of virus morphogenesis as key regulators of the viral life cycle. ..
- Seki S, Kawada M, Takeda A, Igarashi H, Sata T, Matano T. Transmission of simian immunodeficiency virus carrying multiple cytotoxic T-lymphocyte escape mutations with diminished replicative ability can result in AIDS progression in rhesus macaques. J Virol. 2008;82:5093-8 pubmed publisher..Our results showed that even such a "crippled" SIV infection can result in persistent viral replication, multiple reversions, and AIDS progression. ..
- Sakuma R, Noser J, Ohmine S, Ikeda Y. Rhesus monkey TRIM5alpha restricts HIV-1 production through rapid degradation of viral Gag polyproteins. Nat Med. 2007;13:631-5 pubmed..This finding demonstrates a cellular factor blocking HIV-1 production by actively degrading a viral protein. Further understanding of this previously unknown restriction mechanism may reveal new targets for future anti-HIV-1 therapy. ..
- Finzi A, Orthwein A, Mercier J, Cohen E. Productive human immunodeficiency virus type 1 assembly takes place at the plasma membrane. J Virol. 2007;81:7476-90 pubmed..These results point towards the PM as being the primary site of productive HIV-1 assembly in cells that also support Gag accumulation in intracellular compartments. ..
- Adamson C, Freed E. Human immunodeficiency virus type 1 assembly, release, and maturation. Adv Pharmacol. 2007;55:347-87 pubmed
- Friedrich T, Valentine L, Yant L, Rakasz E, Piaskowski S, Furlott J, et al. Subdominant CD8+ T-cell responses are involved in durable control of AIDS virus replication. J Virol. 2007;81:3465-76 pubmed..It is likely that subdominant CD8+ T-cell populations play a key role in maintaining this control. ..
- Goepfert P, Lumm W, Farmer P, Matthews P, Prendergast A, Carlson J, et al. Transmission of HIV-1 Gag immune escape mutations is associated with reduced viral load in linked recipients. J Exp Med. 2008;205:1009-17 pubmed publisher..In addition to their direct implications for HIV-1 vaccine design, these data suggest that CTL-induced viral polymorphisms and their associated in vivo viral fitness costs could have a significant impact on HIV-1 pathogenesis. ..
- Huber M, Fischer M, Misselwitz B, Manrique A, Kuster H, Niederost B, et al. Complement lysis activity in autologous plasma is associated with lower viral loads during the acute phase of HIV-1 infection. PLoS Med. 2006;3:e441 pubmed
- Sacha J, Giraldo Vela J, Buechler M, Martins M, Maness N, Chung C, et al. Gag- and Nef-specific CD4+ T cells recognize and inhibit SIV replication in infected macrophages early after infection. Proc Natl Acad Sci U S A. 2009;106:9791-6 pubmed publisher..These results suggest that retrovirus-specific CD4(+) T cells may contribute directly to elite control by inhibiting viral replication in macrophages. ..
- Ferre A, Hunt P, Critchfield J, Young D, Morris M, Garcia J, et al. Mucosal immune responses to HIV-1 in elite controllers: a potential correlate of immune control. Blood. 2009;113:3978-89 pubmed publisher..These responses may play an important role in mucosal immune surveillance, as suggested by their relative enrichment among persons who control HIV in the absence of therapy. ..
- Lopez Verges S, Camus G, Blot G, Beauvoir R, Benarous R, Berlioz Torrent C. Tail-interacting protein TIP47 is a connector between Gag and Env and is required for Env incorporation into HIV-1 virions. Proc Natl Acad Sci U S A. 2006;103:14947-52 pubmed
- Matthews P, Prendergast A, Leslie A, Crawford H, Payne R, Rousseau C, et al. Central role of reverting mutations in HLA associations with human immunodeficiency virus set point. J Virol. 2008;82:8548-59 pubmed publisher..The significance of these results is in highlighting the rationale for an HIV vaccine that can induce these broad responses. ..
- Ribet D, Harper F, Dewannieux M, Pierron G, Heidmann T. Murine MusD retrotransposon: structure and molecular evolution of an "intracellularized" retrovirus. J Virol. 2007;81:1888-98 pubmed
- Hearps A, Jans D. Regulating the functions of the HIV-1 matrix protein. AIDS Res Hum Retroviruses. 2007;23:341-6 pubmed..J Virol 2005;79:13028-13036) confirms the importance of this protein for HIV infection and highlights a potentially new avenue in multivalent drug therapy. ..
- Casazza J, Betts M, Price D, Precopio M, Ruff L, Brenchley J, et al. Acquisition of direct antiviral effector functions by CMV-specific CD4+ T lymphocytes with cellular maturation. J Exp Med. 2006;203:2865-77 pubmed..Thus, mature CMV-specific CD4+ T cells exhibit distinct functional properties reminiscent of antiviral CD8+ T lymphocytes. ..
- Fischer W, Perkins S, Theiler J, Bhattacharya T, Yusim K, Funkhouser R, et al. Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants. Nat Med. 2007;13:100-6 pubmed
- Chatel Chaix L, Abrahamyan L, Fréchina C, Mouland A, DesGroseillers L. The host protein Staufen1 participates in human immunodeficiency virus type 1 assembly in live cells by influencing pr55Gag multimerization. J Virol. 2007;81:6216-30 pubmed..Our results indicate that Stau1 influences HIV-1 assembly by modulating pr55Gag-pr55Gag interactions, as shown in a live cell interaction assay. This likely occurs when Stau1 interacts with membrane-associated assembly intermediates. ..
- Nchinda G, Kuroiwa J, Oks M, Trumpfheller C, Park C, Huang Y, et al. The efficacy of DNA vaccination is enhanced in mice by targeting the encoded protein to dendritic cells. J Clin Invest. 2008;118:1427-36 pubmed publisher..The efficacy of DNA vaccines therefore may be enhanced by inclusion of sequences such as single-chain antibodies to target the antigen to DCs. ..
- Kim E, Veazey R, Zahn R, McEvers K, Baumeister S, Foster G, et al. Contribution of CD8+ T cells to containment of viral replication and emergence of mutations in Mamu-A*01-restricted epitopes in Simian immunodeficiency virus-infected rhesus monkeys. J Virol. 2008;82:5631-5 pubmed publisher..These results confirm the importance of cytotoxic T cells in controlling viremia and the constraint on epitope sequences that require compensatory changes to go to fixation...
- Smith M, Asher T, Venturi V, Davenport M, Douek D, Price D, et al. Limited maintenance of vaccine-induced simian immunodeficiency virus-specific CD8 T-cell receptor clonotypes after virus challenge. J Virol. 2008;82:7357-68 pubmed publisher..These findings have implications for future AIDS virus vaccine studies, which should consider the "fitness" of vaccine-induced T cells in order to generate robust responses in the face of virus exposure. ..
- Jäger S, Gottwein E, Kräusslich H. Ubiquitination of human immunodeficiency virus type 1 Gag is highly dependent on Gag membrane association. J Virol. 2007;81:9193-201 pubmed..We therefore propose that membrane association and multimerization of HIV-1 Gag proteins, rather than a specific motif within Gag, trigger recognition by the cellular ubiquitination machinery. ..
- Almeida J, Price D, Papagno L, Arkoub Z, Sauce D, Bornstein E, et al. Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover. J Exp Med. 2007;204:2473-85 pubmed..Such attributes are interlinked and constitute the basis for effective control of HIV-1 replication. These data on the features of effective CD8+ T cells in HIV infection may aid in the development of successful T cell vaccines. ..
- Bansal A, Yue L, Conway J, Yusim K, Tang J, Kappes J, et al. Immunological control of chronic HIV-1 infection: HLA-mediated immune function and viral evolution in adolescents. AIDS. 2007;21:2387-97 pubmed..These data suggest that viral fitness costs associated with CD8 T-cell pressure is an important factor determining differences in the viral load among HIV-infected patients. ..
- Matthews P, Leslie A, Katzourakis A, Crawford H, Payne R, Prendergast A, et al. HLA footprints on human immunodeficiency virus type 1 are associated with interclade polymorphisms and intraclade phylogenetic clustering. J Virol. 2009;83:4605-15 pubmed publisher..In conclusion, these data highlight the fact that HLA can be a strong selection force for both intra- and interclade HIV evolution at a population level. ..
- Trumpfheller C, Caskey M, Nchinda G, Longhi M, Mizenina O, Huang Y, et al. The microbial mimic poly IC induces durable and protective CD4+ T cell immunity together with a dendritic cell targeted vaccine. Proc Natl Acad Sci U S A. 2008;105:2574-9 pubmed publisher..We suggest that poly IC be tested as an adjuvant with DC-targeted vaccines to induce numerous multifunctional CD4(+) Th1 cells with proliferative capacity. ..
- Wright E, Schooler J, Ding H, Kieffer C, Fillmore C, Sundquist W, et al. Electron cryotomography of immature HIV-1 virions reveals the structure of the CA and SP1 Gag shells. EMBO J. 2007;26:2218-26 pubmed..This model suggests why the SP1 spacer is essential for assembly of the Gag lattice and how cleavage between SP1 and CA acts as a structural switch controlling maturation. ..
- Klein K, Reed J, Lingappa J. Intracellular destinies: degradation, targeting, assembly, and endocytosis of HIV Gag. AIDS Rev. 2007;9:150-61 pubmed..Thus, the challenge for the future will be to understand which cellular factors act during the pathway from Gag synthesis to assembly, and exactly where and how they act in this pathway. ..
- Jin J, Sturgeon T, Chen C, Watkins S, Weisz O, Montelaro R. Distinct intracellular trafficking of equine infectious anemia virus and human immunodeficiency virus type 1 Gag during viral assembly and budding revealed by bimolecular fluorescence complementation assays. J Virol. 2007;81:11226-35 pubmed publisher..Taken together, our results suggest that lentivirus assembly and budding are regulated by the RNA nuclear export pathway and that alternative cellular pathways can be adapted for lentiviral Gag assembly and budding...
- Crawford H, Prado J, Leslie A, Hue S, Honeyborne I, Reddy S, et al. Compensatory mutation partially restores fitness and delays reversion of escape mutation within the immunodominant HLA-B*5703-restricted Gag epitope in chronic human immunodeficiency virus type 1 infection. J Virol. 2007;81:8346-51 pubmed..These data may help explain the observed association between HLA-B*5703 and long-term control of viremia. ..
- Lee S, Joshi A, Nagashima K, Freed E, Hurley J. Structural basis for viral late-domain binding to Alix. Nat Struct Mol Biol. 2007;14:194-9 pubmed..Overexpression of the V domain inhibits HIV-1 release from cells. This inhibition of release is reversed by mutations that block binding of the Alix V domain to p6. ..
- Honeyborne I, Prendergast A, Pereyra F, Leslie A, Crawford H, Payne R, et al. Control of human immunodeficiency virus type 1 is associated with HLA-B*13 and targeting of multiple gag-specific CD8+ T-cell epitopes. J Virol. 2007;81:3667-72 pubmed..These data are consistent with data from studies of other HLA-class I alleles associated with HIV control that have shown that the targeting of multiple Gag epitopes is associated with relative suppression of viremia. ..
- Datta S, Zhao Z, Clark P, Tarasov S, Alexandratos J, Campbell S, et al. Interactions between HIV-1 Gag molecules in solution: an inositol phosphate-mediated switch. J Mol Biol. 2007;365:799-811 pubmed..As Gag is an extended rod in immature virions, this apparent proximity of the ends in solution implies that it undergoes a major conformational change during particle assembly. ..
- Ono A, Waheed A, Freed E. Depletion of cellular cholesterol inhibits membrane binding and higher-order multimerization of human immunodeficiency virus type 1 Gag. Virology. 2007;360:27-35 pubmed..Altogether, these results are consistent with the hypothesis that cholesterol-enriched membrane microdomains promote HIV-1 particle production by facilitating both Gag-membrane binding and Gag multimerization. ..
- Roy B, Hu J, Guo X, Russell R, Guo F, Kleiman L, et al. Association of RNA helicase a with human immunodeficiency virus type 1 particles. J Biol Chem. 2006;281:12625-35 pubmed..Therefore, RHA represents the first example of cellular RNA helicases that participate in HIV-1 particle production and promote viral reverse transcription. ..
- Arruda L, Sim D, Chikhlikar P, Maciel M, Akasaki K, August J, et al. Dendritic cell-lysosomal-associated membrane protein (LAMP) and LAMP-1-HIV-1 gag chimeras have distinct cellular trafficking pathways and prime T and B cell responses to a diverse repertoire of epitopes. J Immunol. 2006;177:2265-75 pubmed..These data indicate that LAMP-1 and DC-LAMP Ag chimeras follow different trafficking pathways, induce distinct modulatory immune responses, and are able to present cryptic epitopes. ..
- Costa L, Chen N, Lopes A, Aguiar R, Tanuri A, Plemenitas A, et al. Interactions between Nef and AIP1 proliferate multivesicular bodies and facilitate egress of HIV-1. Retrovirology. 2006;3:33 pubmed..We conclude that by binding GagPol and AIP1, Nef not only proliferates MVBs but also contributes to the egress of viral particles from infected cells. ..
- Yao Y, Nellåker C, Karlsson H. Evaluation of minor groove binding probe and Taqman probe PCR assays: Influence of mismatches and template complexity on quantification. Mol Cell Probes. 2006;20:311-6 pubmed
- Bailey J, Williams T, Siliciano R, Blankson J. Maintenance of viral suppression in HIV-1-infected HLA-B*57+ elite suppressors despite CTL escape mutations. J Exp Med. 2006;203:1357-69 pubmed..Continued viral suppression probably reflects CTL responses against unmutated epitopes and residual or de novo responses against epitopes with escape mutations. ..
- Grigorov B, Arcanger F, Roingeard P, Darlix J, Muriaux D. Assembly of infectious HIV-1 in human epithelial and T-lymphoblastic cell lines. J Mol Biol. 2006;359:848-62 pubmed
- Saad J, Miller J, Tai J, Kim A, Ghanam R, Summers M. Structural basis for targeting HIV-1 Gag proteins to the plasma membrane for virus assembly. Proc Natl Acad Sci U S A. 2006;103:11364-9 pubmed..Our findings indicate that PI(4,5)P(2) acts as both a trigger of the myristyl switch and a membrane anchor and suggest a potential mechanism for targeting Gag to membrane rafts. ..
- Booth A, Fang Y, Fallon J, Yang J, Hildreth J, Gould S. Exosomes and HIV Gag bud from endosome-like domains of the T cell plasma membrane. J Cell Biol. 2006;172:923-35 pubmed..In support of this, we find that Jurkat T cells direct the key budding factor of HIV, HIV Gag, to these endosome-like domains of plasma membrane and secrete HIV Gag from the cell in exosomes. ..