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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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Evolution of HIV-1 coreceptor usage during the progression of the disease. In most individuals HIV-1 infection is initially sustained by CCR5-using variants (R5, blue). In ~50% of the patients infected with subtype-B HIV-1, the CCR5-using variants acquire the ability to use CXCR4 (R5X4, blue/red) prior to AIDS diagnosis. Subsequently, these dual-tropic R5X4 variants may lose their ability to use CCR5 (X4 variants, red). Over time, viral coreceptor usage evolves resulting in viral variants with increased affinity for their respective coreceptor (increased color intensity).
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Figure 2: Evolution of HIV-1 coreceptor usage during the progression of the disease. In most individuals HIV-1 infection is initially sustained by CCR5-using variants (R5, blue). In ~50% of the patients infected with subtype-B HIV-1, the CCR5-using variants acquire the ability to use CXCR4 (R5X4, blue/red) prior to AIDS diagnosis. Subsequently, these dual-tropic R5X4 variants may lose their ability to use CCR5 (X4 variants, red). Over time, viral coreceptor usage evolves resulting in viral variants with increased affinity for their respective coreceptor (increased color intensity).

Mentions: During the asymptomatic phase of HIV-1 infection a homogeneous R5 virus population is commonly present that generally has the ability to replicate efficiently in both T cells and macrophages [70,71]. In many patients, a typical pattern of viral evolution has been documented during the course of the infection with the emergence, usually in concomitance with the earliest signs of disease progression, of CXCR4-using variants. However, this pattern is not consistently observed in all patients progressing to AIDS (Figure 2). For example, in patients infected with subtype-B HIV-1, variants that use CXCR4 can be isolated from approximately half of the patients who have developed AIDS [15,24,33,106-109]. Of note, such variants may first appear during the asymptomatic phase of infection, before AIDS is diagnosed [106], albeit after an initial decline of CD4+ T cells [110]. Patients progressing to AIDS often harbor viral populations that can use multiple coreceptors including CCR5, CXCR4 and one or more minor coreceptors [15]. Whether a promiscuous coreceptor usage provides a selective advantage for HIV remains uncertain since most of the minor coreceptors show a low and/or tissue-specific expression pattern.


Clinical significance of HIV-1 coreceptor usage.

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

Evolution of HIV-1 coreceptor usage during the progression of the disease. In most individuals HIV-1 infection is initially sustained by CCR5-using variants (R5, blue). In ~50% of the patients infected with subtype-B HIV-1, the CCR5-using variants acquire the ability to use CXCR4 (R5X4, blue/red) prior to AIDS diagnosis. Subsequently, these dual-tropic R5X4 variants may lose their ability to use CCR5 (X4 variants, red). Over time, viral coreceptor usage evolves resulting in viral variants with increased affinity for their respective coreceptor (increased color intensity).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Evolution of HIV-1 coreceptor usage during the progression of the disease. In most individuals HIV-1 infection is initially sustained by CCR5-using variants (R5, blue). In ~50% of the patients infected with subtype-B HIV-1, the CCR5-using variants acquire the ability to use CXCR4 (R5X4, blue/red) prior to AIDS diagnosis. Subsequently, these dual-tropic R5X4 variants may lose their ability to use CCR5 (X4 variants, red). Over time, viral coreceptor usage evolves resulting in viral variants with increased affinity for their respective coreceptor (increased color intensity).
Mentions: During the asymptomatic phase of HIV-1 infection a homogeneous R5 virus population is commonly present that generally has the ability to replicate efficiently in both T cells and macrophages [70,71]. In many patients, a typical pattern of viral evolution has been documented during the course of the infection with the emergence, usually in concomitance with the earliest signs of disease progression, of CXCR4-using variants. However, this pattern is not consistently observed in all patients progressing to AIDS (Figure 2). For example, in patients infected with subtype-B HIV-1, variants that use CXCR4 can be isolated from approximately half of the patients who have developed AIDS [15,24,33,106-109]. Of note, such variants may first appear during the asymptomatic phase of infection, before AIDS is diagnosed [106], albeit after an initial decline of CD4+ T cells [110]. Patients progressing to AIDS often harbor viral populations that can use multiple coreceptors including CCR5, CXCR4 and one or more minor coreceptors [15]. Whether a promiscuous coreceptor usage provides a selective advantage for HIV remains uncertain since most of the minor coreceptors show a low and/or tissue-specific expression pattern.

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