Caister Academic Press

SHIV Model of Disease

Tatsuhiko Igarashi
from: Lentiviruses and Macrophages: Molecular and Cellular Interactions (Edited by: Moira Desport). Caister Academic Press, U.K. (2010)


Simian-human immunodeficiency virus (SHIV) was generated as an animal model for acquired immunodeficiency syndrome (AIDS) in order to overcome the narrow host range of human immunodeficiency virus (HIV-1). The first-generation SHIVs were nonpathogenic but evolved through animal-to-animal passage to become highly pathogenic viruses. In macaque monkeys, highly pathogenic SHIVs induce a distinct disease phenotype: a massive, systemic, and irreversible depletion of CD4+ T cells occurs within weeks of infection, followed by AIDS-like clinical manifestations. During the acute phase of infection, the virus predominantly infects and destroys CD4+ T cells. As a result, macrophages become the major virus-producing cell type. Virus isolated during the macrophage phase of infection exhibits macrophage tropism, a property not possessed by the inoculum SHIV. The V1/V2 region of the env gene was found to be responsible for the expanded cell tropism observed in the macrophage-tropic virus. The viral entry coreceptor, CXCR4, was maintained during the evolution of the virus. The vast majority of macrophage -tropic viruses are attenuated when inoculated into immune-competent monkeys read more ...
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