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Clinical significance of HIV-1 coreceptor usage.

Schuitemaker H, van 't Wout AB, Lusso P - J Transl Med (2011)

Bottom Line: The physiological basis for the phenotypic variability of HIV-1 was elucidated with the discovery of distinct coreceptors employed by the virus to infect susceptible cells.The role of the viral phenotype in the variable clinical course and treatment outcome of HIV-1 infection has been extensively investigated over the past two decades.In this review, we summarize the major findings on the clinical significance of the HIV-1 coreceptor usage.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, and Center for Infection and Immunity Amsterdam (CINIMA) at the Academic Medical Center of the University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. H.Schuitemaker@amc.uva.nl

ABSTRACT
The identification of phenotypically distinct HIV-1 variants with different prevalence during the progression of the disease has been one of the earliest discoveries in HIV-1 biology, but its relevance to AIDS pathogenesis remains only partially understood. The physiological basis for the phenotypic variability of HIV-1 was elucidated with the discovery of distinct coreceptors employed by the virus to infect susceptible cells. The role of the viral phenotype in the variable clinical course and treatment outcome of HIV-1 infection has been extensively investigated over the past two decades. In this review, we summarize the major findings on the clinical significance of the HIV-1 coreceptor usage.

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Overview of coreceptor use and cell tropism of different HIV-1 variants. Individual viral isolates are classified based on their ability to use CCR5 (R5 variants), CXCR4 (X4 variants) or both coreceptors (R5X4 variants). Bulk viral isolates capable of using both coreceptors are designated dual/mixed (D/M) as their quasispecies may contain any mixture of the various phenotypic variants. The cell tropism of each viral isolate is determined by the expression levels of CCR5 and CXCR4 on the various target cells.
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Figure 1: Overview of coreceptor use and cell tropism of different HIV-1 variants. Individual viral isolates are classified based on their ability to use CCR5 (R5 variants), CXCR4 (X4 variants) or both coreceptors (R5X4 variants). Bulk viral isolates capable of using both coreceptors are designated dual/mixed (D/M) as their quasispecies may contain any mixture of the various phenotypic variants. The cell tropism of each viral isolate is determined by the expression levels of CCR5 and CXCR4 on the various target cells.

Mentions: Although several chemokine receptors may function as HIV-1 coreceptors in vitro, multiple lines of clinical and experimental evidence indicate that only two of them, CCR5 and CXCR4, have bona fide clinical relevance (reviewed in [3]). Both CCR5 and CXCR4 are expressed, in combination with CD4, on all the relevant target cells for HIV-1, including primary CD4+ T cells, macrophages and dendritic cells. Individual viral isolates are presently classified based on their ability to use CCR5 (R5 variants), CXCR4 (X4 variants) or both coreceptors (R5X4 variants) [4]). The dual-tropic R5X4 viruses are further classified as Dual-R (R5X4 variants with more efficient use of CCR5 than of CXCR4) or Dual-X (R5X4 with more efficient use of CXCR4 than of CCR5) [5-7]. In the absence of a more accurate characterization, bulk viral isolates capable of using both coreceptors are designated dual/mixed (D/M) as their quasispecies may contain any mixture of the various phenotypic variants (Figure 1).


Clinical significance of HIV-1 coreceptor usage.

Schuitemaker H, van 't Wout AB, Lusso P - J Transl Med (2011)

Overview of coreceptor use and cell tropism of different HIV-1 variants. Individual viral isolates are classified based on their ability to use CCR5 (R5 variants), CXCR4 (X4 variants) or both coreceptors (R5X4 variants). Bulk viral isolates capable of using both coreceptors are designated dual/mixed (D/M) as their quasispecies may contain any mixture of the various phenotypic variants. The cell tropism of each viral isolate is determined by the expression levels of CCR5 and CXCR4 on the various target cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3105505&req=5

Figure 1: Overview of coreceptor use and cell tropism of different HIV-1 variants. Individual viral isolates are classified based on their ability to use CCR5 (R5 variants), CXCR4 (X4 variants) or both coreceptors (R5X4 variants). Bulk viral isolates capable of using both coreceptors are designated dual/mixed (D/M) as their quasispecies may contain any mixture of the various phenotypic variants. The cell tropism of each viral isolate is determined by the expression levels of CCR5 and CXCR4 on the various target cells.
Mentions: Although several chemokine receptors may function as HIV-1 coreceptors in vitro, multiple lines of clinical and experimental evidence indicate that only two of them, CCR5 and CXCR4, have bona fide clinical relevance (reviewed in [3]). Both CCR5 and CXCR4 are expressed, in combination with CD4, on all the relevant target cells for HIV-1, including primary CD4+ T cells, macrophages and dendritic cells. Individual viral isolates are presently classified based on their ability to use CCR5 (R5 variants), CXCR4 (X4 variants) or both coreceptors (R5X4 variants) [4]). The dual-tropic R5X4 viruses are further classified as Dual-R (R5X4 variants with more efficient use of CCR5 than of CXCR4) or Dual-X (R5X4 with more efficient use of CXCR4 than of CCR5) [5-7]. In the absence of a more accurate characterization, bulk viral isolates capable of using both coreceptors are designated dual/mixed (D/M) as their quasispecies may contain any mixture of the various phenotypic variants (Figure 1).

Bottom Line: The physiological basis for the phenotypic variability of HIV-1 was elucidated with the discovery of distinct coreceptors employed by the virus to infect susceptible cells.The role of the viral phenotype in the variable clinical course and treatment outcome of HIV-1 infection has been extensively investigated over the past two decades.In this review, we summarize the major findings on the clinical significance of the HIV-1 coreceptor usage.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, and Center for Infection and Immunity Amsterdam (CINIMA) at the Academic Medical Center of the University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. H.Schuitemaker@amc.uva.nl

ABSTRACT
The identification of phenotypically distinct HIV-1 variants with different prevalence during the progression of the disease has been one of the earliest discoveries in HIV-1 biology, but its relevance to AIDS pathogenesis remains only partially understood. The physiological basis for the phenotypic variability of HIV-1 was elucidated with the discovery of distinct coreceptors employed by the virus to infect susceptible cells. The role of the viral phenotype in the variable clinical course and treatment outcome of HIV-1 infection has been extensively investigated over the past two decades. In this review, we summarize the major findings on the clinical significance of the HIV-1 coreceptor usage.

Show MeSH
Related in: MedlinePlus