Quantitative analyses reveal distinct sensitivities of the capture of HIV-1 primary viruses and pseudoviruses to broadly neutralizing antibodies

Jiae Kim, Ousman Jobe, Kristina K. Peachman, Nelson L. Michael, Merlin L. Robb, Mangala Rao*, Venigalla B. Rao

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Development of vaccines capable of eliciting broadly neutralizing antibodies (bNAbs) is a key goal to controlling the global AIDS epidemic. To be effective, bNAbs must block the capture of HIV-1 to prevent viral acquisition and establishment of reservoirs. However, the role of bNAbs, particularly during initial exposure of primary viruses to host cells, has not been fully examined. Using a sensitive, quantitative, and high-throughput qRT-PCR assay, we found that primary viruses were captured by host cells and converted into a trypsin-resistant form in less than five minutes. We discovered, unexpectedly, that bNAbs did not block primary virus capture, although they inhibited the capture of pseudoviruses/IMCs and production of progeny viruses at 48 h. Further, viruses escaped bNAb inhibition unless the bNAbs were present in the initial minutes of exposure of virus to host cells. These findings will have important implications for HIV-1 vaccine design and determination of vaccine efficacy.

Original languageEnglish
Pages (from-to)188-198
Number of pages11
JournalVirology
Volume508
DOIs
StatePublished - Aug 2017
Externally publishedYes

Keywords

  • A3R5.7 cells
  • Broadly neutralizing antibodies
  • HIV-1 transmission
  • HIV-1 vaccine
  • Viral capture
  • Virus entry
  • qRT‐PCR

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