共查询到20条相似文献，搜索用时 15 毫秒
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Nef protein of HIV-1 is a transcriptional repressor of HIV-1 LTR 总被引：73，自引：0，他引：73
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Fidelity of HIV-1 reverse transcriptase 总被引：70，自引：0，他引：70
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Bonhoeffer S Chappey C Parkin NT Whitcomb JM Petropoulos CJ 《Science (New York, N.Y.)》2004,306(5701):1547-1550
Reproductive strategies such as sexual reproduction and recombination that involve the shuffling of parental genomes for the production of offspring are ubiquitous in nature. However, their evolutionary benefit remains unclear. Many theories have identified potential benefits, but progress is hampered by the scarcity of relevant data. One class of theories is based on the assumption that mutations affecting fitness exhibit negative epistasis. Retroviruses recombine frequently and thus provide a unique opportunity to test these theories. Using amino acid sequence data and fitness values from 9466 human immunodeficiency virus 1 (HIV-1) isolates, we find in contrast to these theories strong statistical evidence for a predominance of positive epistasis in HIV-1. 相似文献
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Derdeyn CA Decker JM Bibollet-Ruche F Mokili JL Muldoon M Denham SA Heil ML Kasolo F Musonda R Hahn BH Shaw GM Korber BT Allen S Hunter E 《Science (New York, N.Y.)》2004,303(5666):2019-2022
Heterosexual transmission accounts for the majority of human immunodeficiency virus-1 (HIV-1) infections worldwide, yet the viral properties that determine transmission fitness or outgrowth have not been elucidated. Here we show, for eight heterosexual transmission pairs, that recipient viruses were monophyletic, encoding compact, glycan-restricted envelope glycoproteins. These viruses were also uniquely sensitive to neutralization by antibody from the transmitting partner. Thus, the exposure of neutralizing epitopes, which are lost in chronic infection because of immune escape, appears to be favored in the newly infected host. This reveals characteristics of the envelope glycoprotein that influence HIV-1 transmission and may have implications for vaccine design. 相似文献
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Gaschen B Taylor J Yusim K Foley B Gao F Lang D Novitsky V Haynes B Hahn BH Bhattacharya T Korber B 《Science (New York, N.Y.)》2002,296(5577):2354-2360
Globally, human immunodeficiency virus-type 1 (HIV-1) is extraordinarily variable, and this diversity poses a major obstacle to AIDS vaccine development. Currently, candidate vaccines are derived from isolates, with the hope that they will be sufficiently cross-reactive to protect against circulating viruses. This may be overly optimistic, however, given that HIV-1 envelope proteins can differ in more than 30% of their amino acids. To contend with the diversity, country-specific vaccines are being considered, but evolutionary relationships may be more useful than regional considerations. Consensus or ancestor sequences could be used in vaccine design to minimize the genetic differences between vaccine strains and contemporary isolates, effectively reducing the extent of diversity by half. 相似文献
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The accuracy of reverse transcriptase from HIV-1 总被引：72，自引：0，他引：72
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Infection of the SCID-hu mouse by HIV-1 总被引：44，自引：0，他引：44
R Namikawa H Kaneshima M Lieberman I L Weissman J M McCune 《Science (New York, N.Y.)》1988,242(4886):1684-1686
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Human immunodeficiency virus type-1 (HIV-1) membrane fusion is promoted by the formation of a trimer-of-hairpins structure that brings the amino- and carboxyl-terminal regions of the gp41 envelope glycoprotein ectodomain into close proximity. Peptides derived from the carboxyl-terminal region (called C-peptides) potently inhibit HIV-1 entry by binding to the gp41 amino-terminal region. To test the converse of this inhibitory strategy, we designed a small protein, denoted 5-Helix, that binds the C-peptide region of gp41. The 5-Helix protein displays potent (nanomolar) inhibitory activity against diverse HIV-1 variants and may serve as the basis for a new class of antiviral agents. The inhibitory activity of 5-Helix also suggests a strategy for generating an HIV-1 neutralizing antibody response that targets the carboxyl-terminal region of the gp41 ectodomain. 相似文献
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Keele BF Van Heuverswyn F Li Y Bailes E Takehisa J Santiago ML Bibollet-Ruche F Chen Y Wain LV Liegeois F Loul S Ngole EM Bienvenue Y Delaporte E Brookfield JF Sharp PM Shaw GM Peeters M Hahn BH 《Science (New York, N.Y.)》2006,313(5786):523-526
Human immunodeficiency virus type 1 (HIV-1), the cause of human acquired immunodeficiency syndrome (AIDS), is a zoonotic infection of staggering proportions and social impact. Yet uncertainty persists regarding its natural reservoir. The virus most closely related to HIV-1 is a simian immunodeficiency virus (SIV) thus far identified only in captive members of the chimpanzee subspecies Pan troglodytes troglodytes. Here we report the detection of SIVcpz antibodies and nucleic acids in fecal samples from wild-living P. t. troglodytes apes in southern Cameroon, where prevalence rates in some communities reached 29 to 35%. By sequence analysis of endemic SIVcpz strains, we could trace the origins of pandemic (group M) and nonpandemic (group N) HIV-1 to distinct, geographically isolated chimpanzee communities. These findings establish P. t. troglodytes as a natural reservoir of HIV-1. 相似文献
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HIV-1 integrates into the host chromosome and persists as a provirus flanked by long terminal repeats (LTRs). To date, treatment regimens primarily target the virus enzymes or virus-cell fusion, but not the integrated provirus. We report here the substrate-linked protein evolution of a tailored recombinase that recognizes an asymmetric sequence within an HIV-1 LTR. This evolved recombinase efficiently excised integrated HIV proviral DNA from the genome of infected cells. Although a long way from use in the clinic, we speculate that this type of technology might be adapted in future antiretroviral therapies, among other possible uses. 相似文献
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Hatziioannou T Princiotta M Piatak M Yuan F Zhang F Lifson JD Bieniasz PD 《Science (New York, N.Y.)》2006,314(5796):95
Because HIV-1 does not infect most nonhuman primates, animal modeling of human HIV infection and AIDS has primarily consisted of experimentally infecting macaques with related simian immunodeficiency viruses (SIVMAC). However, the usefulness of such models is limited by the substantial divergence between SIVMAC and HIV-1. We derived an HIV-1-based virus that includes only small portions of SIVMAC yet replicates robustly in both transformed and primary rhesus macaque T cells. Derivation of simian-tropic HIV-1 (stHIV-1) has important implications for understanding primate lentivirus zoonosis and should allow the development of improved animal models for studies of AIDS and the evaluation of vaccines and treatments. 相似文献
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Antibody-enhanced infection by HIV-1 via Fc receptor-mediated entry 总被引：49，自引：0，他引：49
Monocytes and macrophages, which may play a central role in the pathogenesis of infection with human immunodeficiency virus type 1 (HIV-1), express the CD4 molecule and Fc receptors (FcR) for immunoglobulin G (IgG). To explore the possibility that FcR mediate HIV-1 infection of monocytes, studies were conducted with the human monocytic cell line U937. These cells were exposed to HIV-1 complexed with various concentrations of serum from HIV-1 antibody-positive individuals and monitored for HIV-1 replication. Serum samples from antibody-negative normal individuals did not affect virus yields. High concentrations of antibody-positive sera showed virus-neutralizing activity; however, cells infected with HIV-1 in the presence of antibody-positive sera at subneutralizing concentrations significantly enhanced virus replication. This infection enhancement was blocked by heat-aggregated gamma-globulin. Moreover, the IgG fraction from an HIV-1 antibody-positive serum enhanced HIV-1 infection at the same serum dilution equivalents. In contrast, IgG-F(ab')2 did not enhance HIV-1 infection but showed neutralizing activity with HIV-1. These results are compatible with the concept of FcR-mediated infection enhancement and suggest that this immunological response to HIV-1, instead of protecting the host, potentially facilitates the infection. 相似文献
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完整而确定的HIV-1整合酶结构在基于受体的抗AIDS药物设计中起着重要的作用。概述了HIV-1整合酶的结构和功能,并从片段结构、模建的全长聚集体以及同源体系3个方面综述了整合酶结构的研究进展。给出了各个代表性体系的应用价值。旨在对HIV-1整合酶抑制剂药物设计及筛选平台的建立提供一定的参考。 相似文献