Defining early SIV replication and dissemination dynamics following vaginal transmission

Claire Deleage, Taina T. Immonen, Christine M. Fennessey, Arnold Reynaldi, Carolyn Reid, Laura Newman, Leslie Lipkey, Timothy E. Schlub, Celine Camus, Sean O'Brien, Jeremy Smedley, Jessica M. Conway, Gregory Q. Del Prete, Miles P. Davenport, Jeffrey D. Lifson, Jacob D. Estes, Brandon F. Keele

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Understanding HIV transmission is critical to guide the development of prophylactic interventions to prevent infection. We used a nonhuman primate (NHP) model with a synthetic swarm of sequence-tagged variants of SIVmac239 ("SIVmac239X") and scheduled necropsy during primary infection (days 3 to 14 after challenge) to study viral dynamics and host responses to the establishment and dissemination of infection following vaginal challenge. We demonstrate that local replication was initiated at multiple sites within the female genital tract (FGT), with each site having multiple viral variants. Local replication and spread in the FGT preceded lymphatic dissemination. Innate viral restriction factors were observed but appeared to follow viral replication and were ineffective at blocking initial viral establishment and dissemination. However, major delays were observed in time to dissemination in animals and among different viral variants within the same animal. It will be important to assess how phenotypic differences affect early viral dynamics.

Original languageEnglish (US)
Article numberaav7116
JournalScience Advances
Volume5
Issue number5
DOIs
StatePublished - Jan 1 2019

ASJC Scopus subject areas

  • Physics and Astronomy (miscellaneous)
  • General

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    Deleage, C., Immonen, T. T., Fennessey, C. M., Reynaldi, A., Reid, C., Newman, L., Lipkey, L., Schlub, T. E., Camus, C., O'Brien, S., Smedley, J., Conway, J. M., Del Prete, G. Q., Davenport, M. P., Lifson, J. D., Estes, J. D., & Keele, B. F. (2019). Defining early SIV replication and dissemination dynamics following vaginal transmission. Science Advances, 5(5), [aav7116]. https://doi.org/10.1126/sciadv.aav7116