HIV is the first pathogenic human retrovirus responsible for a lethal disease of pandemic proportions. Its ability to integrate in the host genome renders its infection life-long, whereas anti-retroviral agents can limit and control its extent but not lead to viral eradication. Its selectivity for CD4+ cells (T lymphocytes, mononuclear phagocytes, and dendritic cells) is biologically sustained by the interaction of its gp120 Env molecule with CD4 itself (primary receptor), which must be followed by binding to a chemokine coreceptor (CCR5 and/or CXCR4) leading to a conformational change of gp41 Env, which causes the fusion between the virion and the cell membrane. A number of intracellular factors have been recently highlighted that control and influence the efficiency of HIV infection in target cells, among which APOBEC3G appears currently as the most relevant or simply best characterized. The virus counteracts these intracellular mechanisms with an array of regulatory and accessory proteins (such as Vif, which inactivates APOBEC3G). After viral integration by means of the reverse transcriptase (RT), several viral (Tat, Rev) and host factors (cytokines, chemokines) control the efficiency of proviral DNA transcription and post-transcriptional steps leading to assembly and release of new progeny virions. Virus replication and pathogenesis occurs mostly in lymphoid organs such as gut-associated lymphoid tissue (GALT) and the central nervous system (CNS), whereas the peripheral blood represents a useful accessible compartment reflective to some extent of organ and tissue events. HIV infection causes a profound depletion of CD4+ T lymphocytes and immunodeficiency that becomes lethal in the stage defined as acquired immunodeficiency syndrome (AIDS). Whether these events are caused directly by viral replication or whether HIV-induced cytopathicity is mostly dependent upon a host immunologic response remains a controversial issue.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)