ABSTRACT
HIV incidence rate is believed to have peaked in the late 1990s and to have stabilized subsequently, notwithstanding an increasing incidence in South-East Asia and China.
Following innoculation of a naive host with biological fluid (e.g. blood, blood products or sexual secretions) containing HIV-1, the virus adheres to cells, e.g. lymphocytes, macrophages and dendritic cells in the blood, lymphoid organs or central nervous system, expressing the CD4 receptor and chemokine coreceptors (e.g the CXC chemokine receptor 4 (CXCR4) and the chemokine receptor 5 (CCR5)). During entry, gp120 attaches to the cell membrane by binding to the CD4 receptor. Subsequent interactions between virus and chemokine co-receptors (e.g. CXCR4 and CCR5) trigger irreversible conformational changes. The fusion event takes place within minutes by pore formation and releases the viral core into the cell cytoplasm. The virus then disassembles and the viral reverse transcriptase produces complementary DNA (cDNA) coded by viral RNA. This viral DNA is then integrated into the host genome by the HIV-1 integrase enzyme. Viral cDNA is then transcribed by the host, producing messenger RNA (mRNA) which is translated into viral peptides. These peptides are then cleaved by HIV protease to form the structural viral proteins that, together with viral RNA, assemble to form new infectious HIV virions. These exit the cell by endosomal budding. Figure 46.1 illustrates the HIV-1 life cycle, together with current and potential therapeutic targets.
