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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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Typical course of HIV-1 disease in relation to HIV-1 coreceptor usage. (A) Individual infected with pure R5 variants: constant rate of CD4 decline and viral load incline. (B) Individual with emergence of CXCR4-using variants in the course of infection: accelerated CD4 decline, viral load incline and disease progression upon emergence of CXCR4-using variants. While CXCR4-using variants can emerge at any stage of infection, untreated individuals who develop such variants progress to AIDS within an average of 2 years after their first detection.
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Figure 3: Typical course of HIV-1 disease in relation to HIV-1 coreceptor usage. (A) Individual infected with pure R5 variants: constant rate of CD4 decline and viral load incline. (B) Individual with emergence of CXCR4-using variants in the course of infection: accelerated CD4 decline, viral load incline and disease progression upon emergence of CXCR4-using variants. While CXCR4-using variants can emerge at any stage of infection, untreated individuals who develop such variants progress to AIDS within an average of 2 years after their first detection.

Mentions: The emergence of CXCR4-using HIV-1 variants in a patient is almost invariably associated with a subsequent increase in the rate of decline of circulating CD4+ T cells, an accelerated disease progression, and a poor prognosis for survival [106] (Figure 3). Indeed, studies in the era preceding the introduction of combination antiretroviral therapy (cART) demonstrated a significant acceleration in the rate of CD4+ T-cell decline after the first detection of CXCR4-using variants [106,107]. However, the presence of CXCR4-using variants is not an obligatory prerequisite for disease progression and a significant proportion of individuals progress to AIDS and AIDS-related death while harboring exclusively R5 HIV-1 variants. Notably, the time from seroconversion to AIDS is not significantly different between individuals who harbor only R5 variants as compared to individuals with detectable CXCR4-using variants (Figure 4).


Clinical significance of HIV-1 coreceptor usage.

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

Typical course of HIV-1 disease in relation to HIV-1 coreceptor usage. (A) Individual infected with pure R5 variants: constant rate of CD4 decline and viral load incline. (B) Individual with emergence of CXCR4-using variants in the course of infection: accelerated CD4 decline, viral load incline and disease progression upon emergence of CXCR4-using variants. While CXCR4-using variants can emerge at any stage of infection, untreated individuals who develop such variants progress to AIDS within an average of 2 years after their first detection.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Typical course of HIV-1 disease in relation to HIV-1 coreceptor usage. (A) Individual infected with pure R5 variants: constant rate of CD4 decline and viral load incline. (B) Individual with emergence of CXCR4-using variants in the course of infection: accelerated CD4 decline, viral load incline and disease progression upon emergence of CXCR4-using variants. While CXCR4-using variants can emerge at any stage of infection, untreated individuals who develop such variants progress to AIDS within an average of 2 years after their first detection.
Mentions: The emergence of CXCR4-using HIV-1 variants in a patient is almost invariably associated with a subsequent increase in the rate of decline of circulating CD4+ T cells, an accelerated disease progression, and a poor prognosis for survival [106] (Figure 3). Indeed, studies in the era preceding the introduction of combination antiretroviral therapy (cART) demonstrated a significant acceleration in the rate of CD4+ T-cell decline after the first detection of CXCR4-using variants [106,107]. However, the presence of CXCR4-using variants is not an obligatory prerequisite for disease progression and a significant proportion of individuals progress to AIDS and AIDS-related death while harboring exclusively R5 HIV-1 variants. Notably, the time from seroconversion to AIDS is not significantly different between individuals who harbor only R5 variants as compared to individuals with detectable CXCR4-using variants (Figure 4).

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