The CCL2 Chemokine Promotes Early Seeding of the Latent HIV Reservoir

• DOI: 10.1101/2021.02.25.432826
• Publication Date: 2021-02-26T03:00:21Z
• Authors: Thomas A. Packard; Roland Schwarzer; Eytan Herzig; Deepashri Rao; Xiaoyu Luo; Johanne H. Egedal; Feng Hsiao; Marek Widera; Judd F. Hultquist; Zachary W. Grimmett; Ronald J. Messer; Nevan J. Krogan; Steven G. Deeks; Nadia R. Roan; Ulf Dittmer; Kim J. Hasenkrug; Warner C. Greene
• Keywords: CCR2; Provirus

ABSTRACT HIV infects long-lived CD4 memory T cells establishing a latent viral reservoir that necessitates lifelong anti-retroviral therapy (ART). How this is formed so swiftly remains unknown. We now show the innate inflammatory response to infection results in CCL2 chemokine release, which can drive recruitment of expressing CCR2 receptor including subset central cells. Supporting role for CCL2/CCR2 axis rapid formation, we find 1) treatment humanized mice with anti-CCL2 antibodies during decreases seeding and 2) CCR2/5+ from blood HIV-infected individuals on long term ART contain significantly more provirus than CCR2/5-negative or naïve Together, these studies support model where host’s recruits zones virus-associated inflammation likely contributing formation reservoir. GRAPHICAL Why established early following infection? An immune occurs acute establishes “zone inflammation” (step 1). The produced part through IFI16 sensing DNA abortively infected promotes 2). Many become productively 3) fraction latently 4). Thus, hijacks host rapidly establish In model, reduction treated infection. Further, harbor substantial detectable proviruses long-term suppressive ART. Abstract Figure