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Phenotypic properties of transmitted founder HIV-1.

Publication ,  Journal Article
Parrish, NF; Gao, F; Li, H; Giorgi, EE; Barbian, HJ; Parrish, EH; Zajic, L; Iyer, SS; Decker, JM; Kumar, A; Hora, B; Berg, A; Cai, F ...
Published in: Proc Natl Acad Sci U S A
April 23, 2013

Defining the virus-host interactions responsible for HIV-1 transmission, including the phenotypic requirements of viruses capable of establishing de novo infections, could be important for AIDS vaccine development. Previous analyses have failed to identify phenotypic properties other than chemokine receptor 5 (CCR5) and CD4+ T-cell tropism that are preferentially associated with viral transmission. However, most of these studies were limited to examining envelope (Env) function in the context of pseudoviruses. Here, we generated infectious molecular clones of transmitted founder (TF; n = 27) and chronic control (CC; n = 14) viruses of subtypes B (n = 18) and C (n = 23) and compared their phenotypic properties in assays specifically designed to probe the earliest stages of HIV-1 infection. We found that TF virions were 1.7-fold more infectious (P = 0.049) and contained 1.9-fold more Env per particle (P = 0.048) compared with CC viruses. TF viruses were also captured by monocyte-derived dendritic cells 1.7-fold more efficiently (P = 0.035) and more readily transferred to CD4+ T cells (P = 0.025). In primary CD4+ T cells, TF and CC viruses replicated with comparable kinetics; however, when propagated in the presence of IFN-α, TF viruses replicated to higher titers than CC viruses. This difference was significant for subtype B (P = 0.000013) but not subtype C (P = 0.53) viruses, possibly reflecting demographic differences of the respective patient cohorts. Together, these data indicate that TF viruses are enriched for higher Env content, enhanced cell-free infectivity, improved dendritic cell interaction, and relative IFN-α resistance. These viral properties, which likely act in concert, should be considered in the development and testing of AIDS vaccines.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

April 23, 2013

Volume

110

Issue

17

Start / End Page

6626 / 6633

Location

United States

Related Subject Headings

  • Virion
  • Viral Envelope Proteins
  • Sequence Analysis, DNA
  • Phenotype
  • Molecular Sequence Data
  • Linear Models
  • Humans
  • HIV-1
  • HIV Infections
  • Enzyme-Linked Immunosorbent Assay
 

Citation

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Parrish, N. F., Gao, F., Li, H., Giorgi, E. E., Barbian, H. J., Parrish, E. H., … Hahn, B. H. (2013). Phenotypic properties of transmitted founder HIV-1. Proc Natl Acad Sci U S A, 110(17), 6626–6633. https://doi.org/10.1073/pnas.1304288110
Parrish, Nicholas F., Feng Gao, Hui Li, Elena E. Giorgi, Hannah J. Barbian, Erica H. Parrish, Lara Zajic, et al. “Phenotypic properties of transmitted founder HIV-1.Proc Natl Acad Sci U S A 110, no. 17 (April 23, 2013): 6626–33. https://doi.org/10.1073/pnas.1304288110.
Parrish NF, Gao F, Li H, Giorgi EE, Barbian HJ, Parrish EH, et al. Phenotypic properties of transmitted founder HIV-1. Proc Natl Acad Sci U S A. 2013 Apr 23;110(17):6626–33.
Parrish, Nicholas F., et al. “Phenotypic properties of transmitted founder HIV-1.Proc Natl Acad Sci U S A, vol. 110, no. 17, Apr. 2013, pp. 6626–33. Pubmed, doi:10.1073/pnas.1304288110.
Parrish NF, Gao F, Li H, Giorgi EE, Barbian HJ, Parrish EH, Zajic L, Iyer SS, Decker JM, Kumar A, Hora B, Berg A, Cai F, Hopper J, Denny TN, Ding H, Ochsenbauer C, Kappes JC, Galimidi RP, West AP, Bjorkman PJ, Wilen CB, Doms RW, O’Brien M, Bhardwaj N, Borrow P, Haynes BF, Muldoon M, Theiler JP, Korber B, Shaw GM, Hahn BH. Phenotypic properties of transmitted founder HIV-1. Proc Natl Acad Sci U S A. 2013 Apr 23;110(17):6626–6633.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

April 23, 2013

Volume

110

Issue

17

Start / End Page

6626 / 6633

Location

United States

Related Subject Headings

  • Virion
  • Viral Envelope Proteins
  • Sequence Analysis, DNA
  • Phenotype
  • Molecular Sequence Data
  • Linear Models
  • Humans
  • HIV-1
  • HIV Infections
  • Enzyme-Linked Immunosorbent Assay