ROLE OF HOST-ENCODED MOLECULES ON HIV VIRIONS

Veterans Medical Research Fdn/San Diego, San Diego CA

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Abstract

DESCRIPTION: This proposal is aimed at elucidating the role and contribution of host-derived cell surface components acquired by HIV-1 progeny virions in HIV infection and pathogenesis. A better understanding of the infection process may assist in vaccine development and therapy as well as providing further insights into the virus replicative cycle. Most enveloped viruses, including the human immunodeficiency virus type-1 (HIV-1), are extruded from the infected cell by budding through cell membranes. The insertion of host cell membrane molecules into the viral particle is likely to occur as the emerging virus is released with part of the host membrane itself. The putative functional role(s) of cellular molecules incorporated into progeny virions requires elucidation as these host-encoded proteins may affect the viral replicative cycle, contribute to transmission and to the overall pathogenesis of the disease. The first part of this proposal is focused on the analysis and identification of signal transduction pathways and host gene expression profiles relevant to the process of infection. These will be gathered following infection of different primary human cell subsets with isogenic progeny viruses bearing on their surfaces specific host-derived molecules (Specific Aim 1). This is a complex phenotype modulated by numerous genes which therefore requires the global approach of high-density microarray. The second part of this research project is centered on the putative modulatory effect(s) the virally embedded host proteins may have on the HIV-1 viral cycle and to assess the effect of virally-embedded host molecules on HIV-1 LTR-driven transcription and virus production (Specifics Aims 2 and 3).