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Review
. 2012 Nov 9;4(11):3020-43.
doi: 10.3390/v4113020.

HIV-1 induced bystander apoptosis

Himanshu Garg  1 , Jonathon Mohl, Anjali Joshi
Affiliations
Review

HIV-1 induced bystander apoptosis

Himanshu Garg et al. Viruses. .

Abstract

Apoptosis of uninfected bystander cells is a key element of HIV pathogenesis and believed to be the driving force behind the selective depletion of CD4+ T cells leading to immunodeficiency. While several viral proteins have been implicated in this process the complex interaction between Env glycoprotein expressed on the surface of infected cells and the receptor and co-receptor expressing bystander cells has been proposed as a major mechanism. HIV-1 utilizes CD4 as the primary receptor for entry into cells; however, it is the viral co-receptor usage that greatly influences CD4 decline and progression to AIDS. This phenomenon is relatively simple for X4 viruses, which arise later during the course of the disease, are considered to be highly fusogenic, and cause a rapid CD4+ T cell decline. However, in contrast, R5 viruses in general have a greater transmissibility, are encountered early during the disease and have a lesser pathogenic potential than the former. The above generalization gets complicated in numerous situations where R5 viruses persist throughout the disease and are capable of causing a rigorous CD4+ T cell decline. This review will discuss the multiple factors that are reported to influence HIV induced bystander apoptosis and pathogenesis including Env glycoprotein phenotype, virus tropism, disease stage, co-receptor expression on CD4+ T cells, immune activation and therapies targeting the viral envelope.

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Figures

Figure 1
Figure 1
Figure depicting the various factors regulating HIV Env fusogencity leading to bystander apoptosis. Top: The fusogenic potential of the HIV Env glycoprotein is determined not only by the HIV subtype but also stage of disease, expression levels of HIV co-receptor in CD4+ T cells in infected individuals and the use of drugs targeting the viral envelope. A complex interplay of the above factors determines the Env fusogenic potential which in turn determines bystander CD4+ T cell death. Bottom: The process of T cell death in HIV infections is initiated by the interactions of Env glycoprotein in infected cells and receptor/co-receptor on neighboring bystander cells. This interaction either leads to full fusion between two interacting cells leading to syncytia formation or an abortive fusion leading to hemifusion. Both the processes eventually lead to cell death via apoptosis.
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