NDLI: Evidence for a cytopathogenicity determinant in HIV-1 Vpr.

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Evidence for a cytopathogenicity determinant in HIV-1 Vpr.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Stevenson, Mario Luzuriaga, Katherine Sullivan, John L. Emerman, Michael Sharkey, Mark Brichacek, Beda Somasundaran, Mohan
Description	Author Affiliation: Somasundaran M ( Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA.);
Abstract	HIV-1 is cytopathic for CD4(+) T lymphocytes in vitro and this property of HIV-1 is generally considered to account for some of its in vivo cytopathogenicity. Thus, the extent of lymphocyte depletion correlates with the level of viremia whereas low levels of viral replication are typically associated with stable lymphocyte levels and asymptomatic infection such as is observed in non-progressors. Here, we describe a non-progressor who did not fit this general pattern in that CD4(+) T lymphocyte homeostasis was maintained in the face of high-level viral replication. Biological viral isolates from this patient replicated in primary lymphocytes without inducing cytopathicity. Because this phenotype is reminiscent of Vpr-deleted viruses, we examined the contribution of the Vpr gene to the viral phenotype. Vpr alleles derived from this patient contained both premature stop codons and an unusual Q3R polymorphism. Insertion of patient-derived Vpr alleles or a Q3R substitution into a cytopathic HIV-1 clone resulted in a marked impairment of cytopathicity without affecting viral replication efficiency. The effect of Vpr on cytopathicity was unrelated to reported activities of Vpr including virion association, interaction with uracil DNA glycosylase, G(2) arrest, or enhancement of macrophage infection but correlated with the ability of Vpr to induce host cell apoptosis. This study suggests the presence of a determinant of in vivo cytopathogenicity within HIV-1 Vpr and further indicates that viral replication can be uncoupled from cytopathicity in vitro and in vivo.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	14
Volume Number	99
Language	English
Publisher	National Academy of Sciences
Publisher Date	2002-07-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cytopathogenic Effect, Viral Physiology Gene Products, Vpr HIV-1 Pathogenicity Alleles Apoptosis Genetics CD4-Positive T-Lymphocytes Pathology Virology Genes, Vpr HIV Infections HIV Long-Term Survivors Isolation & Purification In Vitro Techniques Mutation Polymorphism, Genetic Vpr Gene Products, Human Immunodeficiency Virus Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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