Productively infected cells are generally thought to arise from HIV infection of activated CD4+ T cells, and these infected activated cells are thought to be a recurring source of latently infected cells when a portion of the population transitions to a resting state. We discovered and report here that productively and latently infected cells can instead originate from direct infection of resting CD4+ T cell populations in lymphoid tissues in Fiebig I, the earliest stage of detectable HIV infection. We found that direct infection of resting CD4+ T cells was correlated with the availability of susceptible target cells in lymphoid tissues largely restricted to resting CD4+ T cells in which expression of pTEFb enabled productive infection, and we documented persistence of HIV-producing resting T cells during antiretroviral therapy (ART). Thus, we provide evidence of a mechanism by which direct infection of resting T cells in lymphoid tissues to generate productively and latently infected cells creates a mechanism by which the productively infected cells can replenish both populations and maintain two sources of virus from which HIV infection can rebound, even if ART is instituted at the earliest stage of detectable infection.
Stephen W. Wietgrefe, Jodi Anderson, Lijie Duan, Peter J. Southern, Paul Zuck, Guoxin Wu, Bonnie J. Howell, Cavan Reilly, Eugène Kroon, Suthat Chottanapund, Supranee Buranapraditkun, Carlo Sacdalan, Nicha Tulmethakaan, Donn J. Colby, Nitiya Chomchey, Peeriya Prueksakaew, Suteeraporn Pinyakorn, Rapee Trichavaroj, Julie L. Mitchell, Lydie Trautmann, Denise Hsu, Sandhya Vasan, Sopark Manasnayakorn, Mark de Souza, Sodsai Tovanabutra, Alexandra Schuetz, Merlin L. Robb, Nittaya Phanuphak, Jintanat Ananworanich, Timothy W. Schacker, Ashley T. Haase, on behalf of the RV254/SEARCH 010 Study Team
This file is in Adobe Acrobat (PDF) format. If you have not installed and configured the Adobe Acrobat Reader on your system.
PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.
Many versions of the free Acrobat Reader do not allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users: Right-click on the Download link and choose the option that says something like "Save Link As...". Mac users should hold the mouse button down on the link to get these same options.