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Primary infection by a human immunodeficiency virus with atypical coreceptor tropism.

Publication ,  Journal Article
Jiang, C; Parrish, NF; Wilen, CB; Li, H; Chen, Y; Pavlicek, JW; Berg, A; Lu, X; Song, H; Tilton, JC; Pfaff, JM; Henning, EA; Decker, JM ...
Published in: J Virol
October 2011

The great majority of human immunodeficiency virus type 1 (HIV-1) strains enter CD4+ target cells by interacting with one of two coreceptors, CCR5 or CXCR4. Here we describe a transmitted/founder (T/F) virus (ZP6248) that was profoundly impaired in its ability to utilize CCR5 and CXCR4 coreceptors on multiple CD4+ cell lines as well as primary human CD4+ T cells and macrophages in vitro yet replicated to very high titers (>80 million RNA copies/ml) in an acutely infected individual. Interestingly, the envelope (Env) glycoprotein of this clade B virus had a rare GPEK sequence in the crown of its third variable loop (V3) rather than the consensus GPGR sequence. Extensive sequencing of sequential plasma samples showed that the GPEK sequence was present in virtually all Envs, including those from the earliest time points after infection. The molecularly cloned (single) T/F virus was able to replicate, albeit poorly, in cells obtained from ccr5Δ32 homozygous donors. The ZP6248 T/F virus could also infect cell lines overexpressing the alternative coreceptors GPR15, APJ, and FPRL-1. A single mutation in the V3 crown sequence (GPEK->GPGK) of ZP6248 restored its infectivity in CCR5+ cells but reduced its ability to replicate in GPR15+ cells, indicating that the V3 crown motif played an important role in usage of this alternative coreceptor. These results suggest that the ZP6248 T/F virus established an acute in vivo infection by using coreceptor(s) other than CCR5 or CXCR4 or that the CCR5 coreceptor existed in an unusual conformation in this individual.

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Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

October 2011

Volume

85

Issue

20

Start / End Page

10669 / 10681

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Virology
  • Viral Tropism
  • Receptors, Peptide
  • Receptors, Lipoxin
  • Receptors, HIV
  • Receptors, G-Protein-Coupled
  • Receptors, Formyl Peptide
  • Macrophages
  • Humans
 

Citation

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MLA
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Jiang, C., Parrish, N. F., Wilen, C. B., Li, H., Chen, Y., Pavlicek, J. W., … Gao, F. (2011). Primary infection by a human immunodeficiency virus with atypical coreceptor tropism. J Virol, 85(20), 10669–10681. https://doi.org/10.1128/JVI.05249-11
Jiang, Chunlai, Nicholas F. Parrish, Craig B. Wilen, Hui Li, Yue Chen, Jeffrey W. Pavlicek, Anna Berg, et al. “Primary infection by a human immunodeficiency virus with atypical coreceptor tropism.J Virol 85, no. 20 (October 2011): 10669–81. https://doi.org/10.1128/JVI.05249-11.
Jiang C, Parrish NF, Wilen CB, Li H, Chen Y, Pavlicek JW, et al. Primary infection by a human immunodeficiency virus with atypical coreceptor tropism. J Virol. 2011 Oct;85(20):10669–81.
Jiang, Chunlai, et al. “Primary infection by a human immunodeficiency virus with atypical coreceptor tropism.J Virol, vol. 85, no. 20, Oct. 2011, pp. 10669–81. Pubmed, doi:10.1128/JVI.05249-11.
Jiang C, Parrish NF, Wilen CB, Li H, Chen Y, Pavlicek JW, Berg A, Lu X, Song H, Tilton JC, Pfaff JM, Henning EA, Decker JM, Moody MA, Drinker MS, Schutte R, Freel S, Tomaras GD, Nedellec R, Mosier DE, Haynes BF, Shaw GM, Hahn BH, Doms RW, Gao F. Primary infection by a human immunodeficiency virus with atypical coreceptor tropism. J Virol. 2011 Oct;85(20):10669–10681.

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

October 2011

Volume

85

Issue

20

Start / End Page

10669 / 10681

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Virology
  • Viral Tropism
  • Receptors, Peptide
  • Receptors, Lipoxin
  • Receptors, HIV
  • Receptors, G-Protein-Coupled
  • Receptors, Formyl Peptide
  • Macrophages
  • Humans