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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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Hypothetical model of the evolutionary dynamics of CXCR4 usage in relation to the age of each HIV-1 subtype epidemic. Recent data suggest that the proportion of patients with detectable emergence of CXCR4-using HIV-1 variants varies in relation to the age of the different subtype epidemics, with subtype D (high CXCR4 switch rate) being the oldest and subtype C (low CXCR4 switch rate) the youngest.
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Figure 5: Hypothetical model of the evolutionary dynamics of CXCR4 usage in relation to the age of each HIV-1 subtype epidemic. Recent data suggest that the proportion of patients with detectable emergence of CXCR4-using HIV-1 variants varies in relation to the age of the different subtype epidemics, with subtype D (high CXCR4 switch rate) being the oldest and subtype C (low CXCR4 switch rate) the youngest.

Mentions: The different prevalence of CXCR4-using variants among different HIV-1 genetic subtypes remains puzzling. As CXCR4-using variants emerge after an accumulation of mutations, the different prevalence observed among different subtypes and CRFs may reflect the same phenomenon at the population level [147], although a direct relationship between evolutionary rate and development of CXCR4 usage has not been specifically investigated. Based on a series of recent observations, however, it is tempting to speculate that the prevalence of CXCR4-using HIV-1 is increasing with the age of the subtype epidemics (Figure 5). Indeed, phylogenetic studies have revealed that the subtype-D epidemic, which has the highest prevalence of CXCR4- using variants, is one of the oldest, while the subtype-C epidemic, which has a much lower prevalence of CXCR4-using variants, is considered one of the most recently emerged [148,149] (UNAIDS). The subtype-B HIV-1 epidemic has an intermediate pattern, both in terms of age and prevalence of CXCR4-using HIV-1 [150]. This assumption is highly speculative and not supported by all the data available at present. However, if confirmed, it would imply that all the subtype epidemics are evolving towards a higher prevalence of CXCR4-using HIV-1 variants although it is conceivable that each epidemic might reach a point of equilibrium beyond which such prevalence will not further increase.


Clinical significance of HIV-1 coreceptor usage.

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

Hypothetical model of the evolutionary dynamics of CXCR4 usage in relation to the age of each HIV-1 subtype epidemic. Recent data suggest that the proportion of patients with detectable emergence of CXCR4-using HIV-1 variants varies in relation to the age of the different subtype epidemics, with subtype D (high CXCR4 switch rate) being the oldest and subtype C (low CXCR4 switch rate) the youngest.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Hypothetical model of the evolutionary dynamics of CXCR4 usage in relation to the age of each HIV-1 subtype epidemic. Recent data suggest that the proportion of patients with detectable emergence of CXCR4-using HIV-1 variants varies in relation to the age of the different subtype epidemics, with subtype D (high CXCR4 switch rate) being the oldest and subtype C (low CXCR4 switch rate) the youngest.
Mentions: The different prevalence of CXCR4-using variants among different HIV-1 genetic subtypes remains puzzling. As CXCR4-using variants emerge after an accumulation of mutations, the different prevalence observed among different subtypes and CRFs may reflect the same phenomenon at the population level [147], although a direct relationship between evolutionary rate and development of CXCR4 usage has not been specifically investigated. Based on a series of recent observations, however, it is tempting to speculate that the prevalence of CXCR4-using HIV-1 is increasing with the age of the subtype epidemics (Figure 5). Indeed, phylogenetic studies have revealed that the subtype-D epidemic, which has the highest prevalence of CXCR4- using variants, is one of the oldest, while the subtype-C epidemic, which has a much lower prevalence of CXCR4-using variants, is considered one of the most recently emerged [148,149] (UNAIDS). The subtype-B HIV-1 epidemic has an intermediate pattern, both in terms of age and prevalence of CXCR4-using HIV-1 [150]. This assumption is highly speculative and not supported by all the data available at present. However, if confirmed, it would imply that all the subtype epidemics are evolving towards a higher prevalence of CXCR4-using HIV-1 variants although it is conceivable that each epidemic might reach a point of equilibrium beyond which such prevalence will not further increase.

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