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 Estes, Brandon F. Keele

Research output: Contribution to journalArticle

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

Fingerprint

infectious diseases
animals
primates
human immunodeficiency virus
constrictions

ASJC Scopus subject areas

  • General
  • Physics and Astronomy (miscellaneous)

Cite this

Deleage, C., Immonen, T. T., Fennessey, C. M., Reynaldi, A., Reid, C., Newman, L., ... 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

Defining early SIV replication and dissemination dynamics following vaginal transmission. / Deleage, Claire; Immonen, Taina T.; Fennessey, Christine M.; Reynaldi, Arnold; Reid, Carolyn; Newman, Laura; Lipkey, Leslie; Schlub, Timothy E.; Camus, Celine; O'Brien, Sean; Smedley, Jeremy; Conway, Jessica M.; Del Prete, Gregory Q.; Davenport, Miles P.; Lifson, Jeffrey D.; Estes, Jacob; Keele, Brandon F.

In: Science Advances, Vol. 5, No. 5, aav7116, 01.01.2019.

Research output: Contribution to journalArticle

Deleage, C, Immonen, TT, Fennessey, CM, Reynaldi, A, Reid, C, Newman, L, Lipkey, L, Schlub, TE, Camus, C, O'Brien, S, Smedley, J, Conway, JM, Del Prete, GQ, Davenport, MP, Lifson, JD, Estes, J & Keele, BF 2019, 'Defining early SIV replication and dissemination dynamics following vaginal transmission', Science Advances, vol. 5, no. 5, aav7116. https://doi.org/10.1126/sciadv.aav7116
Deleage C, Immonen TT, Fennessey CM, Reynaldi A, Reid C, Newman L et al. Defining early SIV replication and dissemination dynamics following vaginal transmission. Science Advances. 2019 Jan 1;5(5). aav7116. https://doi.org/10.1126/sciadv.aav7116
Deleage, Claire ; Immonen, Taina T. ; Fennessey, Christine M. ; Reynaldi, Arnold ; Reid, Carolyn ; Newman, Laura ; Lipkey, Leslie ; Schlub, Timothy E. ; Camus, Celine ; O'Brien, Sean ; Smedley, Jeremy ; Conway, Jessica M. ; Del Prete, Gregory Q. ; Davenport, Miles P. ; Lifson, Jeffrey D. ; Estes, Jacob ; Keele, Brandon F. / Defining early SIV replication and dissemination dynamics following vaginal transmission. In: Science Advances. 2019 ; Vol. 5, No. 5.
@article{6f73eee7959646c9bb1ae546dfbe71c4,
title = "Defining early SIV replication and dissemination dynamics following vaginal transmission",
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.",
author = "Claire Deleage and Immonen, {Taina T.} and Fennessey, {Christine M.} and Arnold Reynaldi and Carolyn Reid and Laura Newman and Leslie Lipkey and Schlub, {Timothy E.} and Celine Camus and Sean O'Brien and Jeremy Smedley and Conway, {Jessica M.} and {Del Prete}, {Gregory Q.} and Davenport, {Miles P.} and Lifson, {Jeffrey D.} and Jacob Estes and Keele, {Brandon F.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1126/sciadv.aav7116",
language = "English (US)",
volume = "5",
journal = "Indian Journal of Pure and Applied Physics",
issn = "0019-5596",
publisher = "National Institute of Science Communication and Information Resources (NISCAIR)",
number = "5",

}

TY - JOUR

T1 - Defining early SIV replication and dissemination dynamics following vaginal transmission

AU - Deleage, Claire

AU - Immonen, Taina T.

AU - Fennessey, Christine M.

AU - Reynaldi, Arnold

AU - Reid, Carolyn

AU - Newman, Laura

AU - Lipkey, Leslie

AU - Schlub, Timothy E.

AU - Camus, Celine

AU - O'Brien, Sean

AU - Smedley, Jeremy

AU - Conway, Jessica M.

AU - Del Prete, Gregory Q.

AU - Davenport, Miles P.

AU - Lifson, Jeffrey D.

AU - Estes, Jacob

AU - Keele, Brandon F.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85066297182&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85066297182&partnerID=8YFLogxK

U2 - 10.1126/sciadv.aav7116

DO - 10.1126/sciadv.aav7116

M3 - Article

VL - 5

JO - Indian Journal of Pure and Applied Physics

JF - Indian Journal of Pure and Applied Physics

SN - 0019-5596

IS - 5

M1 - aav7116

ER -