Abstract
Human immunodeficiency virus type I (HIV-1) infects target cells through interaction with the CD4 molecule and chemokine receptors, mainly CCR5 and CXCR4. Viral isolates can be phenotypically classified based on the co-receptor they utilize to infect target cells. Thus, R5 and X4 virus use respectively CCR5 and CXCR4, whereas R5X4 virus can use either CCR5 or CXCR4. This review describes the central role played by co-receptor expression and usage for HIV-1 cell tropism, transmission and pathogenesis. We discuss various hypotheses proposed to explain the preferential transmission of R5 viruses and the mechanisms driving the change of HIV-1 co-receptor usage in the course of infection. Recent insights in the intrinsic variability of R5 viruses and their role in influencing disease progression in both adults and children are also discussed.
Highlights
Human immunodeficiency virus type 1 (HIV-1) entry into the host cell is dependent upon binding of the virus envelope protein to the cellular receptor CD4 and a co-receptor, generally the chemokine receptors CCR5 or CXCR4
Additional evidences that a co-receptor for HIV-1 entry was required, derived from the observation that HIV1 exhibited in vitro distinct cellular tropism for CD4+ human target cells, CD4+ T cells and macrophages, which brought to a first attempt of classification of HIV1 as T cell line tropic (TCL-tropic) and Macrophagetropic (M-tropic)
Karlsson et al deeply explored the intrinsic variability of the replication capacity and the sensitivity to β-chemokines of R5 viruses. They infected a panel of U87.CD4 cells expressing a series of chimeric receptors between CCR5 and CXCR4 with R5 viruses obtained from HIV-1 infected individuals throughout disease progression [29]
Summary
Human immunodeficiency virus type 1 (HIV-1) entry into the host cell is dependent upon binding of the virus envelope protein (env) to the cellular receptor CD4 and a co-receptor, generally the chemokine receptors CCR5 or CXCR4. The identification of chemokine receptors as the co-receptors of HIV-1 improved our understanding of the pathogenesis of HIV-1 infection with respect to the mechanism of viral entry, viral tropism and differences in disease course among infected individuals. CXCR4-using virus variants evolve in about one-half of subtype B infected individuals, and their emergence is associated with an accelerated course of the disease. Discuss the chemokine receptor used by HIV-1 to infect target cells, their relevance to define viral tropism, their involvement in viral transmission, viral phenotypic evolution and disease progression both in adult and paediatric HIV-1 infected patients
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