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Chapter 3 : Steps Involved in HIV:Cell Interaction and Virus Entry
Transmission of HIV requires the successful interaction of the virus with receptors on a cell surface. The sites on the virus and on the cells that are involved in this interaction, and the events required for viral entry, are reviewed in this chapter. The CD4 molecule may have a role in viral infection aside from its binding to the HIV envelope. Several early studies examining the role of the CD4:virus interaction in HIV infection indicated that the CD4 receptor alone was neither sufficient nor the sole means for viral entry. The identification of CXCR4 as an HIV coreceptor occurred shortly before other investigators began examining chemokine receptors in HIV infection. Certain cytokines can increase or decrease chemokine receptor expression, thus influencing virus infection and selection. Enveloped viruses, such as HIV, following attachment, enter cells after fusion with the cell membrane. Thus, three major steps can be involved in infection: attachment, fusion, and entry. The fusion process can be measured by membrane fluorescence dequenching. Investigators have shown that after attachment to CD4 a delay in viral entry at the cell surface can influence the spread of HIV and the extent of virus production. The chapter talks about down-modulation of the CD4 protein, infection of cells lacking CD4 expression, cell surface interactions, other possible mechanisms Involved in virus entry, and cell-to-cell transfer of HIV. The spread of HIV in the host results from production of infectious progeny and also by cell-to-cell transfer of virus and possibly by non-envelope-mediated processes.