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Recent key advances in human immunodeficiency virus medicine and implications for China.

ABSTRACT: In this article we summarize several recent major developments in human immunodeficiency virus treatment, prevention, outcome, and social policy change. Updated international guidelines endorse more aggressive treatment strategies and safer antiretroviral drugs. New antiretroviral options are being tested. Important lessons were learned in the areas of human immunodeficiency virus vaccines and microbicide gels from clinical studies, and additional trials in prevention, especially pre-exposure prophylaxis, are nearing completion. Insight into the role of the virus in the pathogenesis of diseases traditionally thought to be unrelated to acquired immunodeficiency syndrome has become a driving force for earlier and universal therapy. Lastly, we review important achievements of and future challenges facing China as she steps into her eighth year of the National Free Antiretroviral Treatment Program.

SUBMITTER: Sun K

PROVIDER: S-EPMC2890503 | biostudies-other | 2010 May

REPOSITORIES: biostudies-other

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Recent key advances in human immunodeficiency virus medicine and implications for China.

Sun Kai K Zhou Shuntai S Chen Ray Y RY Cohen Myron S MS Zhang Fujie F

AIDS research and therapy 20100526

In this article we summarize several recent major developments in human immunodeficiency virus treatment, prevention, outcome, and social policy change. Updated international guidelines endorse more aggressive treatment strategies and safer antiretroviral drugs. New antiretroviral options are being tested. Important lessons were learned in the areas of human immunodeficiency virus vaccines and microbicide gels from clinical studies, and additional trials in prevention, especially pre-exposure pr ...[more]

PMID: 20500898

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Project description:The simian hemorrhagic fever virus (SHFV) genome differs from those of other members of the family Arteriviridae in encoding three papain-like one proteases (PLP1?, PLP1? and PLP1?) at the 5' end and two adjacent sets of four minor structural proteins at the 3' end. The catalytic Cys and His residues and cleavage sites for each of the SHFV PLP1s were predicted and their functionality was tested in in vitro transcription/translation reactions done with wildtype or mutant polyprotein constructs. Mass spectrometry analyses of selected autoproteolytic products confirmed cleavage site locations. The catalytic Cys of PLP1? is unusual in being adjacent to an Ala instead of a Typ. PLP1? cleaves at both downstream and upstream sites. Intermediate precursor and alternative cleavage products were detected in the in vitro transcription/translation reactions but only the three mature nsp1 proteins were detected in SHFV-infected MA104 cell lysates with SHFV nsp1 protein-specific antibodies. The duplicated sets of SHFV minor structural proteins were predicted to be functionally redundant. A stable, full-length, infectious SHFV-LVR cDNA clone was constructed and a set of mutant infectious clones was generated each with the start codon of one of the minor structural proteins mutated. All eight of the minor structural proteins were found to be required for production of infectious extracellular virus. SHFV causes a fatal hemorrhagic fever in macaques but asymptomatic, persistent infections in natural hosts such as baboons. SHFV infections were compared in macrophages and myeloid dendritic cells from baboons and macaques. Virus yields were higher from macaque cells than from baboon cells. Macrophage cultures from the two types of animals differed dramatically in the percentage of cells infected. In contrast, similar percentages of myeloid dendritic cells were infected but virus replication was efficient in the macaque cells but inefficient in the baboon cells. SHFV infection induced the production of pro-inflammatory cytokines, including IL-1?, IL-6, IL-12/23(p40), TNF-? and MIP-1?, in macaque cells but not baboon cells.

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Recent key advances in human immunodeficiency virus medicine and implications for China.

Publications

Recent key advances in human immunodeficiency virus medicine and implications for China.

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