Lucy A McNamara1, Kathleen L Collins. 1. Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Abstract
PURPOSE OF REVIEW: Although latent HIV-1 infection in CD4+ T cells contributes to HIV persistence, there is mounting evidence that other viral reservoirs exist. Here, we review recent data suggesting that the infection of hematopoietic progenitor cells creates additional reservoirs for HIV in vivo. RECENT FINDINGS: New studies suggest that some types of hematopoietic progenitor cells have the potential to generate reservoirs for HIV. This review focuses on two types that can be infected by HIV in vitro and in vivo: multipotent hematopoietic progenitor cells in the bone marrow and circulating mast cell progenitors. Of these two types, only CD34+ bone marrow cells have been shown to harbor latent provirus in HIV-positive individuals with undetectable viral loads on highly active antiretroviral therapy (HAART). Latent infection of these long-lived cell types may create a significant barrier to HIV eradication; the infection of hematopoietic stem cells in particular could lead to an HIV reservoir that does not appreciably decay over the lifespan of the host. SUMMARY: To eradicate HIV infection, it will be necessary to purge all viral reservoirs in the host. The findings highlighted here suggest that multipotent hematopoietic progenitor cells and possibly tissue mast cells may constitute significant reservoirs for HIV that must be addressed in order to eliminate HIV infection. Future studies are needed to determine which types of CD34+ cells are infected in vivo and whether infected CD34+ cells contribute to residual viremia in people with undetectable viral loads on HAART.
PURPOSE OF REVIEW: Although latent HIV-1 infection in CD4+ T cells contributes to HIV persistence, there is mounting evidence that other viral reservoirs exist. Here, we review recent data suggesting that the infection of hematopoietic progenitor cells creates additional reservoirs for HIV in vivo. RECENT FINDINGS: New studies suggest that some types of hematopoietic progenitor cells have the potential to generate reservoirs for HIV. This review focuses on two types that can be infected by HIV in vitro and in vivo: multipotent hematopoietic progenitor cells in the bone marrow and circulating mast cell progenitors. Of these two types, only CD34+ bone marrow cells have been shown to harbor latent provirus in HIV-positive individuals with undetectable viral loads on highly active antiretroviral therapy (HAART). Latent infection of these long-lived cell types may create a significant barrier to HIV eradication; the infection of hematopoietic stem cells in particular could lead to an HIV reservoir that does not appreciably decay over the lifespan of the host. SUMMARY: To eradicate HIV infection, it will be necessary to purge all viral reservoirs in the host. The findings highlighted here suggest that multipotent hematopoietic progenitor cells and possibly tissue mast cells may constitute significant reservoirs for HIV that must be addressed in order to eliminate HIV infection. Future studies are needed to determine which types of CD34+ cells are infected in vivo and whether infected CD34+ cells contribute to residual viremia in people with undetectable viral loads on HAART.
Authors: Janet D Siliciano; Joleen Kajdas; Diana Finzi; Thomas C Quinn; Karen Chadwick; Joseph B Margolick; Colin Kovacs; Stephen J Gange; Robert F Siliciano Journal: Nat Med Date: 2003-05-18 Impact factor: 53.440
Authors: Beda Joos; Marek Fischer; Herbert Kuster; Satish K Pillai; Joseph K Wong; Jürg Böni; Bernard Hirschel; Rainer Weber; Alexandra Trkola; Huldrych F Günthard Journal: Proc Natl Acad Sci U S A Date: 2008-10-20 Impact factor: 11.205
Authors: B Ramratnam; J E Mittler; L Zhang; D Boden; A Hurley; F Fang; C A Macken; A S Perelson; M Markowitz; D D Ho Journal: Nat Med Date: 2000-01 Impact factor: 53.440
Authors: T W Chun; L Stuyver; S B Mizell; L A Ehler; J A Mican; M Baseler; A L Lloyd; M A Nowak; A S Fauci Journal: Proc Natl Acad Sci U S A Date: 1997-11-25 Impact factor: 11.205
Authors: K S Slobod; T A Bennett; P J Freiden; A M Kechli; N Howlett; P M Flynn; D R Head; D K Srivastava; J M Boyett; M K Brenner; J V Garcia Journal: Blood Date: 1996-11-01 Impact factor: 22.113
Authors: T F Neal; H K Holland; C M Baum; F Villinger; A A Ansari; R Saral; J R Wingard; W H Fleming Journal: Blood Date: 1995-09-01 Impact factor: 22.113
Authors: J Bruce Sundstrom; Gregory A Hair; Aftab A Ansari; W Evan Secor; Alasdair M Gilfillan; Dean D Metcalfe; Arnold S Kirshenbaum Journal: J Immunol Date: 2009-05-15 Impact factor: 5.422
Authors: Caroline E Mullis; Amy E Oliver; Leigh Anne Eller; David Guwatudde; Amy C Mueller; Michael A Eller; Hannah Kibuuka; Merlin Robb; Thomas C Quinn; Andrew D Redd Journal: AIDS Res Hum Retroviruses Date: 2012-02-02 Impact factor: 2.205
Authors: Christine M Durand; Gabriel Ghiaur; Janet D Siliciano; S Alireza Rabi; Evelyn E Eisele; Maria Salgado; Liang Shan; Jun F Lai; Hao Zhang; Joseph Margolick; Richard J Jones; Joel E Gallant; Richard F Ambinder; Robert F Siliciano Journal: J Infect Dis Date: 2012-01-24 Impact factor: 5.226
Authors: Nirzari Parikh; Michael R Nonnemacher; Vanessa Pirrone; Timothy Block; Anand Mehta; Brian Wigdahl Journal: Curr HIV Res Date: 2012-10 Impact factor: 1.581
Authors: Olivia O'Connell; Alexander Repik; Jacqueline D Reeves; Maria Paz Gonzalez-Perez; Briana Quitadamo; Elizabeth D Anton; Maria Duenas-Decamp; Paul Peters; Rongheng Lin; Susan Zolla-Pazner; Davide Corti; Aaron Wallace; Shixia Wang; Xiang-Peng Kong; Shan Lu; Paul R Clapham Journal: J Virol Date: 2012-10-10 Impact factor: 5.103
Authors: Xin Shi; Matthew D Sims; Michel M Hanna; Ming Xie; Peter G Gulick; Yong-Hui Zheng; Marc D Basson; Ping Zhang Journal: Int Rev Immunol Date: 2014-03-21 Impact factor: 5.311
Authors: Paul J Bryce; Rustom Falahati; Laurie L Kenney; John Leung; Christopher Bebbington; Nenad Tomasevic; Rebecca A Krier; Chia-Lin Hsu; Leonard D Shultz; Dale L Greiner; Michael A Brehm Journal: J Allergy Clin Immunol Date: 2016-04-06 Impact factor: 10.793