Accession Number : ADA321113

Title :   Quantitative Assessment of HIV Replication and Variation In Vivo: Relevance to Disease Pathogenesis and Response to Therapy.

Descriptive Note : Final rept. 22 Jun 93-31 Dec 95,

Corporate Author : ALABAMA UNIV IN BIRMINGHAM

Personal Author(s) : Shaw, George M.

PDF Url : ADA321113

Report Date : DEC 1996

Pagination or Media Count : 145

Abstract : The pathogenesis of HIV-1 disease is driven by continuous rounds of viral replication in lymphoreticular tissues. Plasma virus load is believed to reflect virus production in these tissue site but the dynamics and quantitative relationships between virus populations the blood and lymphoid tissues remain to be determined. In the studies described, we have developed quantitative approaches for evaluating plasma viral RNA content and composition. We show that plasma viral RNA is virion-associated, is correlated with plasma viral p24 antigen and infectivity titers, and can be accurately quantified by RT-PCR and branched DNA (bDNA) signal amplification assays. Furthermore, we show that initiation of potent antiretroviral therapy, or initiation of a cytotoxic T-lymphocyte (CTL) response in primary (acute) infection, leads to rapid declines in plasma virus load and replacement of wild-type virus populations by escape variants. Importantly, the studies show for the first time that virus-specific CTL exert a biologically significant suppressive effect on UrV-l replication in vivo, comparable in magnitude to the effects of antiretroviral chemotherapy. Plasma virus was shown to have a half- life (Ty) of 6 hours, virus-producing lymphocytes a TV2 of 2 days, and latently infected cells a TV2 of 10-21 days. These data provide a quantitative and dynamic assessment of H(V-1 replication in vivo and provide insight into the biological activity of antiretroviral drugs and the host immune system in natural infection.

Descriptors :   *TISSUES(BIOLOGY), *DEOXYRIBONUCLEIC ACIDS, *INFECTIOUS DISEASES, *HUMAN IMMUNODEFICIENCY VIRUSES, *IN VIVO ANALYSIS, *LYMPHATIC SYSTEM, BIOLOGY, PLASMAS(PHYSICS), POPULATION, THERAPY, AMPLIFICATION, RESPONSE(BIOLOGY), DRUGS, VIRUSES, ESCAPE SYSTEMS, RIBONUCLEIC ACIDS, PATHOGENESIS, POTENCY, BLOOD, ACQUIRED IMMUNE DEFICIENCY SYNDROME, CHEMOTHERAPY, RETROVIRUSES.

Subject Categories : Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE