A minor population of macrophage-tropic HIV-1 variants is identified in recrudescing viremia following analytic treatment interruption
Por:
Andrade, VM, Mavian, C, Babic, D, Cordeiro, T, Sharkey, M, Barrios, L, Brander, C, Martinez-Picado, J, Dalmau, J, Llano, A, Li, JZ, Jacobson, J, Lavine, CL, Seaman, MS, Salemi, M and Stevenson, M
Publicada:
5 may 2020
Ahead of Print:
16 abr 2020
Resumen:
HIV-1 persists in cellular reservoirs that can reignite viremia if anti-retroviral therapy (ART) is interrupted. Therefore, insight into the nature of those reservoirs may be revealed from the composition of recrudescing viremia following treatment cessation. A minor population of macrophage-tropic (M-tropic) viruses was identified in a library of recombinant viruses constructed with individual envelope genes that were obtained from plasma of six individuals undergoing analytic treatment interruption (ATI). M-tropic viruses could also be enriched from post-ATI plasma using macrophage-specific (CD14) but not CD4+ T cell-specific (CD3) antibodies, suggesting that M-tropic viruses had a macrophage origin. Molecular clock analysis indicated that the establishment of M-tropic HIV-1 variants predated ATI. Collectively, these data suggest that macrophages are a viral reservoir in HIV-1-infected individuals on effective ART and that M-tropic variants can appear in rebounding viremia when treatment is interrupted. These findings have implications for the design of curative strategies for HIV-1.
Filiaciones:
Andrade, VM:
Univ Miami, Miller Sch Med, Mol Cell & Dev Biol, Miami, FL 33136 USA
Mavian, C:
Univ Florida, Emerging Pathogens Inst, Gainesville, FL 32610 USA
Babic, D:
Univ Miami, Miller Sch Med, Dept Med, Miami, FL 33136 USA
Cordeiro, T:
Univ Miami, Miller Sch Med, Dept Med, Miami, FL 33136 USA
Sharkey, M:
Univ Miami, Miller Sch Med, Dept Med, Miami, FL 33136 USA
Barrios, L:
Univ Miami, Miller Sch Med, Dept Med, Miami, FL 33136 USA
:
Inst Recerca Sida, Badalona 08916, Spain
:
Inst Recerca Sida, Badalona 08916, Spain
:
Inst Recerca Sida, Badalona 08916, Spain
:
Inst Recerca Sida, Badalona 08916, Spain
Li, JZ:
Harvard Med Sch, Brigham & Womens Hosp, Boston, MA 02115 USA
Jacobson, J:
Temple Univ, Lewis Katz Sch Med, Philadelphia, PA 19122 USA
Lavine, CL:
Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA
Seaman, MS:
Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA
Salemi, M:
Univ Florida, Emerging Pathogens Inst, Gainesville, FL 32610 USA
Stevenson, M:
Univ Miami, Miller Sch Med, Dept Med, Miami, FL 33136 USA
Univ Miami, Dept Med, Div Infect Dis, Miller Sch Med, Miami, FL 33136 USA
Green Published, Bronze
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