Mode of Infection

 

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HIV is an enveloped human retrovirus. The virion contains two copies of the RNA genome and three key enzymes; protease, integrase, and reverse transcriptase. The inner core of HIV consists of the p24 and p17 capsid proteins. Clinical diagnosis of HIV infection involves detection of serum antibodies directed against the p24 capsid protein. The capsid is surrounded by the viral envelope, which is acquired when a nascent virion buds from an infected cell. As the virus leaves the cell, it is enveloped by the cellular membrane. Protruding from the envelope is the viral glycoprotein, gp160. gp160 is made up of two component parts, gp120 and gp41, both of which play important roles in attachment and penetration of HIV into target cells.

Graphic obtained fromScientific American 1988. Vol. 259

 

The infection process begins when gp120 binds to the principle receptor on the target cell, CD4. This induces conformational changes within the gp120 protein which exposes a binding site for a coreceptor. Many strains of HIV-1 exist, but most fit into one of two categories. HIV strains which efficiently infect T cells are referred to as T-cell tropic and preferentially utilize the chemokine receptor CXCR4 as the coreceptor . Other strains of HIV which efficiently infect cells of the monocyte/macrophage lineage are referred to as macrophage tropic and preferentially utilize the chemokine receptor CCR5 as the coreceptor . Binding to the coreceptor induces additional conformational changes within gp120 which exposes the fusogenic gp41 domain. This results in fusion of the viral envelope with the target cell membrane . The gp120-chemokine receptor binding event is an essential part of the infection process. This is exemplified by a small cohort of people who remain uninfected despite multiple exposures to HIV. These individuals possess a homozygous mutation of the CCR5 gene, which prevents the CCR5 receptor from being presented at the cell surface. This mutation renders these individuals virtually resistant to infection by macrophage tropic strains of HIV.

Once the viral envelope has fused with the target cell membrane, the contents of the virion enter the host cell and infection is achieved. The reverse transcriptase enzyme then copies the viral genomic RNA into DNA. Next, the DNA copy of the viral genome is readily transported to the nucleus and subsequently integrated into the host cell genomic DNA by the integrase enzyme. Once integration is completed, viral genes can be transcribed by host cell polymerases into viral mRNA, and consequently translated into viral proteins. The next step is virion assembly, followed by processing of the capsid proteins by the viral protease. At this point, the nascent virions are able to bud from the host cell in search of new target cells to infect.

Fields, B.N., et al., 1996. Fundamental Virology

 

Question regarding this page should be directed to: Becky_Schweighardt@Brown.edu

 

References

Deng, H., et al., 1996. Identification of a major coreceptor for primary isolates of HIV-1. Nature 381:661-666.

Feng, Y., et al., 1996. HIV-1 entry cofactor: Functional cDNA cloning of a seven-transmembrane G protein coupled receptor. Science 272:872-877.

Fields, B.N., et al., 1996. Fundamental Virology, Lippincott-Raven Publishers, Philadelphia.

Kwong, P.D. et al, 1998. Structure of an HIV gp120 envelope glycoprotein structure involved in complex with the CD4 receptor and a neutralizing human antibody. Nature 393:648-659.

Liu, R., et al., 1996. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply exposed individuals to HIV-1 infection. Cell 86:367-377.

Mims, Playfair, Roitt, Wakelin, and Williams, 1998. Medical Microbiology, Mosby International Publishers Limited, London.

 

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