Simian immunodeficiency virus persistence in cellular and anatomic reservoirs in antiretroviral therapy-suppressed infant rhesus macaques

Maud Mavigner, Jakob Habib, Claire Deleage, Elias Rosen, Cameron Mattingly, Katherine Bricker, Angela Kashuba, Franck Amblard, Raymond F. Schinazi, Sherrie Jean, Joyce Cohen, Colleen McGary, Mirko Paiardini, Matthew P. Wood, Donald L. Sodora, Guido Silvestri, Jacob Estes, Ann Chahroudi

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Worldwide, nearly two million children are infected with human immunodeficiency virus (HIV), with breastfeeding accounting for the majority of contemporary HIV transmissions. Antiretroviral therapy (ART) has reduced HIV-related morbidity and mortality but is not curative. The main barrier to a cure is persistence of latent HIV in long-lived reservoirs. However, our understanding of the cellular and anatomic sources of the HIV reservoir during infancy and childhood is limited. Here, we developed a pediatric model of ART suppression in orally simian immunodeficiency virus (SIV)-infected rhesus macaque (RM) infants, with measurement of virus persistence in blood and tissues after 6 to 9 months of ART. Cross-sectional analyses were conducted to compare SIV RNA and DNA levels in adult and infant RMs naive to treatment and on ART. We demonstrate efficient viral suppression following ART initiation in SIV-infected RM infants with sustained undetectable plasma viral loads in the setting of heterogeneous penetration of ART into lymphoid and gastrointestinal tissues and low drug levels in the brain. We further show reduction in SIV RNA and DNA on ART in lymphoid tissues of both infant and adult RMs but stable (albeit low) levels of SIV RNA and DNA in the brains of viremic and ART-suppressed infants. Finally, we report a large contribution of naive CD4+ T cells to the total CD4 reservoir of SIV in blood and lymph nodes of ART-suppressed RM infants that differs from what we show in adults. These results reveal important aspects of HIV/SIV persistence in infants and provide insight into strategic targets for cure interventions in a pediatric population.

Original languageEnglish (US)
Article numbere00562
JournalJournal of virology
Volume92
Issue number18
DOIs
StatePublished - Sep 1 2018

Keywords

  • Antiretroviral therapy
  • Infants
  • Rhesus macaques
  • SIV

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Fingerprint Dive into the research topics of 'Simian immunodeficiency virus persistence in cellular and anatomic reservoirs in antiretroviral therapy-suppressed infant rhesus macaques'. Together they form a unique fingerprint.

  • Cite this

    Mavigner, M., Habib, J., Deleage, C., Rosen, E., Mattingly, C., Bricker, K., Kashuba, A., Amblard, F., Schinazi, R. F., Jean, S., Cohen, J., McGary, C., Paiardini, M., Wood, M. P., Sodora, D. L., Silvestri, G., Estes, J., & Chahroudi, A. (2018). Simian immunodeficiency virus persistence in cellular and anatomic reservoirs in antiretroviral therapy-suppressed infant rhesus macaques. Journal of virology, 92(18), [e00562]. https://doi.org/10.1128/JVI.00562-18