Contribution of intact viral genomes persisting in blood and tissues during ART to plasma viral rebound in SHIV-infected rhesus macaques

César Trifone; Corentin Richard; Amélie Pagliuzza; Caroline Dufour; Audrée Lemieux; Natasha M Clark; Sanath K Janaka; Christine M Fennessey; Brandon E Keele; Rémi Fromentin; Jacob D Estes; Daniel E Kaufmann; Andrés Finzi; David T Evans; Nicolas Chomont

doi:10.1016/j.isci.2025.111998

Contribution of intact viral genomes persisting in blood and tissues during ART to plasma viral rebound in SHIV-infected rhesus macaques

iScience. 2025 Feb 11;28(3):111998. doi: 10.1016/j.isci.2025.111998. eCollection 2025 Mar 21.

Authors

César Trifone^{1

2}, Corentin Richard³, Amélie Pagliuzza¹, Caroline Dufour¹, Audrée Lemieux¹, Natasha M Clark⁴, Sanath K Janaka⁴, Christine M Fennessey⁵, Brandon E Keele⁵, Rémi Fromentin^{1

2}, Jacob D Estes^{6

7}, Daniel E Kaufmann^{1

2

8

9}, Andrés Finzi^{1

2}, David T Evans⁴, Nicolas Chomont^{1

2}

Affiliations

¹ Centre de Recherche du CHUM, Montréal, QC H2X 0A9, Canada.
² Département de Microbiologie, infectiologie et immunologie, Faculté de Médecine, Université de Montréal, Montréal, QC H3T 1J4, Canada.
³ University College of London, London, England WC1E 6BT, UK.
⁴ Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53707, USA.
⁵ AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA.
⁶ Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97239, USA.
⁷ Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97239, USA.
⁸ Département de Médecine, Université de Montréal, Montréal, QC H3T 1J4, Canada.
⁹ Division of Infectious Diseases, Department of Medicine, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland.

Abstract

Persistent SIV/HIV reservoirs are the primary obstacle to a cure and the source of viral rebound after ART interruption (ATI). However, the anatomical source of viral rebound remains elusive. Here, we characterized the proviral landscape in the blood, inguinal, and axillary lymph nodes and colon biopsies of five SHIV-infected rhesus macaques (RMs), under ART for 28 weeks. From the 144 near full-length (NFL) proviral sequences obtained pre-ATI, 35% were genetically intact and only 2.8% were found in multiple copies. Envelope sequences of plasma rebounding viruses after ATI, more frequently matched pre-ATI intact proviruses retrieved from lymph nodes compared to sequences isolated from the blood or the colon (4, 1, and 1 pair of matched sequences, respectively). Our results suggest that clonal expansion of infected cells rare in this model, and that intact proviruses persisting in the lymph nodes may be a preferential source of viral rebound upon ATI.

Keywords: Genomics; Virology.