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Frequent CXCR4 tropism of HIV-1 subtype A and CRF02_AG during late-stage disease - indication of an evolving epidemic in West Africa

Esbjörnsson, Joakim LU ; Månsson, Fredrik LU ; Martinez Arias, Wilma LU ; Vincic, Elzbieta LU ; Biague, Antonio J.; da Silva, Zacarias J.; Fenyö, Eva Maria LU ; Norrgren, Hans LU and Medstrand, Patrik LU (2010) In Retrovirology 7.
Abstract
Background: HIV-1 is one of the fastest evolving pathogens, and is distinguished by geographic and genetic variants that have been classified into different subtypes and circulating recombinant forms (CRFs). Early in infection the primary coreceptor is CCR5, but during disease course CXCR4-using HIV-1 populations may emerge. This has been correlated with accelerated disease progression in HIV-1 subtype B. Basic knowledge of HIV-1 coreceptor tropism is important due to the recent introduction of coreceptor antagonists in antiretroviral therapy, and subtype-specific differences regarding how frequently HIV-1 CXCR4-using populations appear in late-stage disease need to be further investigated. To study how frequently CXCR4-using populations... (More)
Background: HIV-1 is one of the fastest evolving pathogens, and is distinguished by geographic and genetic variants that have been classified into different subtypes and circulating recombinant forms (CRFs). Early in infection the primary coreceptor is CCR5, but during disease course CXCR4-using HIV-1 populations may emerge. This has been correlated with accelerated disease progression in HIV-1 subtype B. Basic knowledge of HIV-1 coreceptor tropism is important due to the recent introduction of coreceptor antagonists in antiretroviral therapy, and subtype-specific differences regarding how frequently HIV-1 CXCR4-using populations appear in late-stage disease need to be further investigated. To study how frequently CXCR4-using populations appear in late-stage disease among HIV-1 subtype A and CRF02_AG, we evaluated the accuracy of a recombinant virus phenotypic assay for these subtypes, and used it to determine the HIV-1 coreceptor tropism of plasma samples collected during late-stage disease in Guinea-Bissau. We also performed a genotypic analysis and investigated subtype-specific differences in the appearance of CXCR4 tropism late in disease. Results: We found that the recombinant virus phenotypic assay accurately predicted HIV-1 coreceptor tropism of subtype A and CRF02_AG. Over the study period (1997-2007), we found an increasing and generally high frequency of CXCR4 tropism (86%) in CRF02_AG. By sequence analysis of the V3 region of our samples we developed a novel genotypic rule for predicting CXCR4 tropism in CRF02_AG, based on the combined criteria of the total number of charged amino acids and net charge. This rule had higher sensitivity than previously described genotypic rules and may be useful for development of future genotypic tools for this CRF. Finally, we conducted a literature analysis, combining data of 498 individuals in late-stage disease, and found high amounts of CXCR4 tropism for all major HIV-1 subtypes (60-77%), except for subtype C (15%). Conclusions: The increase in CXCR4 tropism over time suggests an evolving epidemic of CRF02_AG. The results of the literature analysis demonstrate the need for further studies investigating subtype-specific emergence for CXCR4-tropism; this may be particularly important due to the introduction of CCR5-antagonists in HIV treatment regimens. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Retrovirology
volume
7
publisher
BioMed Central
external identifiers
  • wos:000276753800002
  • scopus:77952572526
ISSN
1742-4690
DOI
10.1186/1742-4690-7-23
language
English
LU publication?
yes
id
57b69787-b369-4300-bfe1-bb19741543a2 (old id 1602012)
date added to LUP
2010-05-19 10:49:11
date last changed
2018-05-29 09:33:18
@article{57b69787-b369-4300-bfe1-bb19741543a2,
  abstract     = {Background: HIV-1 is one of the fastest evolving pathogens, and is distinguished by geographic and genetic variants that have been classified into different subtypes and circulating recombinant forms (CRFs). Early in infection the primary coreceptor is CCR5, but during disease course CXCR4-using HIV-1 populations may emerge. This has been correlated with accelerated disease progression in HIV-1 subtype B. Basic knowledge of HIV-1 coreceptor tropism is important due to the recent introduction of coreceptor antagonists in antiretroviral therapy, and subtype-specific differences regarding how frequently HIV-1 CXCR4-using populations appear in late-stage disease need to be further investigated. To study how frequently CXCR4-using populations appear in late-stage disease among HIV-1 subtype A and CRF02_AG, we evaluated the accuracy of a recombinant virus phenotypic assay for these subtypes, and used it to determine the HIV-1 coreceptor tropism of plasma samples collected during late-stage disease in Guinea-Bissau. We also performed a genotypic analysis and investigated subtype-specific differences in the appearance of CXCR4 tropism late in disease. Results: We found that the recombinant virus phenotypic assay accurately predicted HIV-1 coreceptor tropism of subtype A and CRF02_AG. Over the study period (1997-2007), we found an increasing and generally high frequency of CXCR4 tropism (86%) in CRF02_AG. By sequence analysis of the V3 region of our samples we developed a novel genotypic rule for predicting CXCR4 tropism in CRF02_AG, based on the combined criteria of the total number of charged amino acids and net charge. This rule had higher sensitivity than previously described genotypic rules and may be useful for development of future genotypic tools for this CRF. Finally, we conducted a literature analysis, combining data of 498 individuals in late-stage disease, and found high amounts of CXCR4 tropism for all major HIV-1 subtypes (60-77%), except for subtype C (15%). Conclusions: The increase in CXCR4 tropism over time suggests an evolving epidemic of CRF02_AG. The results of the literature analysis demonstrate the need for further studies investigating subtype-specific emergence for CXCR4-tropism; this may be particularly important due to the introduction of CCR5-antagonists in HIV treatment regimens.},
  author       = {Esbjörnsson, Joakim and Månsson, Fredrik and Martinez Arias, Wilma and Vincic, Elzbieta and Biague, Antonio J. and da Silva, Zacarias J. and Fenyö, Eva Maria and Norrgren, Hans and Medstrand, Patrik},
  issn         = {1742-4690},
  language     = {eng},
  publisher    = {BioMed Central},
  series       = {Retrovirology},
  title        = {Frequent CXCR4 tropism of HIV-1 subtype A and CRF02_AG during late-stage disease - indication of an evolving epidemic in West Africa},
  url          = {http://dx.doi.org/10.1186/1742-4690-7-23},
  volume       = {7},
  year         = {2010},
}