Phenotypic properties of transmitted founder HIV-1

Nicholas F. Parrish, Feng Gao, Hui Li, Elena E. Giorgi, Hannah J. Barbian, Erica H. Parrish, Lara Zajic, Shilpa S. Iyer, Julie M. Decker, Amit Kumar, Bhavna Hora, Anna Berg, Fangping Caic, Jennifer Hopper, Thomas N. Denny, Haitao Ding, Christina Ochsenbauer, John C. Kappes, Rachel P. Galimidi, Anthony P. WestPamela J. Bjorkman, Craig B. Wilen, Robert W. Doms, Meagan O'Brien, Nina Bhardwaj, Persephone Borrow, Barton F. Haynes, Mark Muldoon, James P. Theiler, Bette Korber, George M. Shaw, Beatrice H. Hahn

Research output: Contribution to journalArticlepeer-review

318 Scopus citations

Abstract

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 pseudovi-ruses. 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.

Original languageEnglish
Pages (from-to)6626-6633
Number of pages8
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number17
DOIs
StatePublished - 23 Apr 2013
Externally publishedYes

Keywords

  • Acute HIV-1 infection
  • Epidemic HIV-1 spread
  • Innate immunity
  • Mucosal HIV-1 transmission

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