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Virus Entry via the Alternative Coreceptors CCR3 and FPRL1 Differs by Human Immunodeficiency Virus Type 1 Subtype.

Nedellec, R; Coetzer, M; Shimizu, N; Hoshino, H; Polonis, V R; Morris, L; Mårtensson, Ulrika LU ; Binley, J; Overbaugh, J and Mosier, D E (2009) In Journal of Virology 83. p.8353-8363
Abstract
HIV-1 infects target cells by binding to CD4 and a chemokine receptor, most commonly CCR5. CXCR4 is a frequent alternative coreceptor (CoR) in subtype B and D HIV-1 infection, but the importance of many other alternative CoR remains elusive. We have analyzed HIV-1 envelope proteins (Env) from 66 individuals infected with the major subtypes of HIV-1 to determine if virus entry into highly permissive NP-2 cell lines expressing most known alternative CoR differed by HIV-1 subtype. We also performed linear regression analysis to determine if virus entry via the major CoR CCR5 correlated with use of any alternative CoR, and if this correlation differed by subtype. Virus pseudotyped with subtype B Env showed robust entry via CCR3 that was highly... (More)
HIV-1 infects target cells by binding to CD4 and a chemokine receptor, most commonly CCR5. CXCR4 is a frequent alternative coreceptor (CoR) in subtype B and D HIV-1 infection, but the importance of many other alternative CoR remains elusive. We have analyzed HIV-1 envelope proteins (Env) from 66 individuals infected with the major subtypes of HIV-1 to determine if virus entry into highly permissive NP-2 cell lines expressing most known alternative CoR differed by HIV-1 subtype. We also performed linear regression analysis to determine if virus entry via the major CoR CCR5 correlated with use of any alternative CoR, and if this correlation differed by subtype. Virus pseudotyped with subtype B Env showed robust entry via CCR3 that was highly correlated with CCR5 entry efficiency. By contrast, viruses pseudotyped with subtype A and C Env were able to use the recently described alternative CoR FPRL1 more efficiently than CCR3, and use of FPRL1 was correlated with CCR5 entry. Subtype D Env was unable to use either CCR3 or FPRL1 efficiently, a unique pattern of alternative CoR use. These results suggest that each subtype of circulating HIV-1 may be subject to somewhat different selective pressures for Env-mediated entry into target cells, and suggest that CCR3 may be used as a surrogate CoR by subtype B while FPRL1 may be used as a surrogate CoR by subtype A and C. These data may provide insight into development of resistance to CCR5-targeted entry inhibitors and alternative entry pathways for each HIV-1 subtype. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Virology
volume
83
pages
8353 - 8363
publisher
American Society for Microbiology
external identifiers
  • WOS:000269122300005
  • PMID:19553323
  • Scopus:69249220260
ISSN
1098-5514
DOI
10.1128/JVI.00780-09
language
English
LU publication?
yes
id
e8f7cf86-4f38-4c0b-838d-e3aa7ba95a03 (old id 1433919)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19553323?dopt=Abstract
date added to LUP
2009-07-06 10:17:10
date last changed
2016-11-13 04:28:49
@misc{e8f7cf86-4f38-4c0b-838d-e3aa7ba95a03,
  abstract     = {HIV-1 infects target cells by binding to CD4 and a chemokine receptor, most commonly CCR5. CXCR4 is a frequent alternative coreceptor (CoR) in subtype B and D HIV-1 infection, but the importance of many other alternative CoR remains elusive. We have analyzed HIV-1 envelope proteins (Env) from 66 individuals infected with the major subtypes of HIV-1 to determine if virus entry into highly permissive NP-2 cell lines expressing most known alternative CoR differed by HIV-1 subtype. We also performed linear regression analysis to determine if virus entry via the major CoR CCR5 correlated with use of any alternative CoR, and if this correlation differed by subtype. Virus pseudotyped with subtype B Env showed robust entry via CCR3 that was highly correlated with CCR5 entry efficiency. By contrast, viruses pseudotyped with subtype A and C Env were able to use the recently described alternative CoR FPRL1 more efficiently than CCR3, and use of FPRL1 was correlated with CCR5 entry. Subtype D Env was unable to use either CCR3 or FPRL1 efficiently, a unique pattern of alternative CoR use. These results suggest that each subtype of circulating HIV-1 may be subject to somewhat different selective pressures for Env-mediated entry into target cells, and suggest that CCR3 may be used as a surrogate CoR by subtype B while FPRL1 may be used as a surrogate CoR by subtype A and C. These data may provide insight into development of resistance to CCR5-targeted entry inhibitors and alternative entry pathways for each HIV-1 subtype.},
  author       = {Nedellec, R and Coetzer, M and Shimizu, N and Hoshino, H and Polonis, V R and Morris, L and Mårtensson, Ulrika and Binley, J and Overbaugh, J and Mosier, D E},
  issn         = {1098-5514},
  language     = {eng},
  pages        = {8353--8363},
  publisher    = {ARRAY(0xa20a120)},
  series       = {Journal of Virology},
  title        = {Virus Entry via the Alternative Coreceptors CCR3 and FPRL1 Differs by Human Immunodeficiency Virus Type 1 Subtype.},
  url          = {http://dx.doi.org/10.1128/JVI.00780-09},
  volume       = {83},
  year         = {2009},
}