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Transmitted/founder and chronic subtype C HIV-1 use CD4 and CCR5 receptors with equal efficiency and are not inhibited by blocking the integrin α4β7.

Publication ,  Journal Article
Parrish, NF; Wilen, CB; Banks, LB; Iyer, SS; Pfaff, JM; Salazar-Gonzalez, JF; Salazar, MG; Decker, JM; Parrish, EH; Berg, A; Hopper, J; Gao, F ...
Published in: PLoS Pathog
2012

Sexual transmission of human immunodeficiency virus type 1 (HIV-1) most often results from productive infection by a single transmitted/founder (T/F) virus, indicating a stringent mucosal bottleneck. Understanding the viral traits that overcome this bottleneck could have important implications for HIV-1 vaccine design and other prevention strategies. Most T/F viruses use CCR5 to infect target cells and some encode envelope glycoproteins (Envs) that contain fewer potential N-linked glycosylation sites and shorter V1/V2 variable loops than Envs from chronic viruses. Moreover, it has been reported that the gp120 subunits of certain transmitted Envs bind to the gut-homing integrin α4β7, possibly enhancing virus entry and cell-to-cell spread. Here we sought to determine whether subtype C T/F viruses, which are responsible for the majority of new HIV-1 infections worldwide, share biological properties that increase their transmission fitness, including preferential α4β7 engagement. Using single genome amplification, we generated panels of both T/F (n = 20) and chronic (n = 20) Env constructs as well as full-length T/F (n = 6) and chronic (n = 4) infectious molecular clones (IMCs). We found that T/F and chronic control Envs were indistinguishable in the efficiency with which they used CD4 and CCR5. Both groups of Envs also exhibited the same CD4+ T cell subset tropism and showed similar sensitivity to neutralization by CD4 binding site (CD4bs) antibodies. Finally, saturating concentrations of anti-α4β7 antibodies failed to inhibit infection and replication of T/F as well as chronic control viruses, although the growth of the tissue culture-adapted strain SF162 was modestly impaired. These results indicate that the population bottleneck associated with mucosal HIV-1 acquisition is not due to the selection of T/F viruses that use α4β7, CD4 or CCR5 more efficiently.

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Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

2012

Volume

8

Issue

5

Start / End Page

e1002686

Location

United States

Related Subject Headings

  • Virus Replication
  • Virus Internalization
  • Virology
  • Viral Tropism
  • Receptors, CCR5
  • Neutralization Tests
  • Mucous Membrane
  • Integrins
  • Humans
  • Host-Pathogen Interactions
 

Citation

APA
Chicago
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MLA
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Parrish, N. F., Wilen, C. B., Banks, L. B., Iyer, S. S., Pfaff, J. M., Salazar-Gonzalez, J. F., … Doms, R. W. (2012). Transmitted/founder and chronic subtype C HIV-1 use CD4 and CCR5 receptors with equal efficiency and are not inhibited by blocking the integrin α4β7. PLoS Pathog, 8(5), e1002686. https://doi.org/10.1371/journal.ppat.1002686
Parrish, Nicholas F., Craig B. Wilen, Lauren B. Banks, Shilpa S. Iyer, Jennifer M. Pfaff, Jesus F. Salazar-Gonzalez, Maria G. Salazar, et al. “Transmitted/founder and chronic subtype C HIV-1 use CD4 and CCR5 receptors with equal efficiency and are not inhibited by blocking the integrin α4β7.PLoS Pathog 8, no. 5 (2012): e1002686. https://doi.org/10.1371/journal.ppat.1002686.
Parrish NF, Wilen CB, Banks LB, Iyer SS, Pfaff JM, Salazar-Gonzalez JF, et al. Transmitted/founder and chronic subtype C HIV-1 use CD4 and CCR5 receptors with equal efficiency and are not inhibited by blocking the integrin α4β7. PLoS Pathog. 2012;8(5):e1002686.
Parrish, Nicholas F., et al. “Transmitted/founder and chronic subtype C HIV-1 use CD4 and CCR5 receptors with equal efficiency and are not inhibited by blocking the integrin α4β7.PLoS Pathog, vol. 8, no. 5, 2012, p. e1002686. Pubmed, doi:10.1371/journal.ppat.1002686.
Parrish NF, Wilen CB, Banks LB, Iyer SS, Pfaff JM, Salazar-Gonzalez JF, Salazar MG, Decker JM, Parrish EH, Berg A, Hopper J, Hora B, Kumar A, Mahlokozera T, Yuan S, Coleman C, Vermeulen M, Ding H, Ochsenbauer C, Tilton JC, Permar SR, Kappes JC, Betts MR, Busch MP, Gao F, Montefiori D, Haynes BF, Shaw GM, Hahn BH, Doms RW. Transmitted/founder and chronic subtype C HIV-1 use CD4 and CCR5 receptors with equal efficiency and are not inhibited by blocking the integrin α4β7. PLoS Pathog. 2012;8(5):e1002686.

Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

2012

Volume

8

Issue

5

Start / End Page

e1002686

Location

United States

Related Subject Headings

  • Virus Replication
  • Virus Internalization
  • Virology
  • Viral Tropism
  • Receptors, CCR5
  • Neutralization Tests
  • Mucous Membrane
  • Integrins
  • Humans
  • Host-Pathogen Interactions