TY - JOUR
T1 - Animal models for studies of HIV-1 brain reservoirs
AU - Waight, Emiko
AU - Zhang, Chen
AU - Mathews, Saumi
AU - Kevadiya, Bhavesh D.
AU - Lloyd, K. C.Kent
AU - Gendelman, Howard E.
AU - Gorantla, Santhi
AU - Poluektova, Larisa Y.
AU - Dash, Prasanta K.
N1 - Publisher Copyright:
© 2022 The Authors. Journal of Leukocyte Biology published by Wiley Periodicals LLC on behalf of Society for Leukocyte Biology.
PY - 2022/11
Y1 - 2022/11
N2 - The HIV-1 often evades a robust antiretroviral-mediated immune response, leading to persistent infection within anatomically privileged sites including the CNS. Continuous low-level infection occurs in the presence of effective antiretroviral therapy (ART) in CD4+ T cells and mononuclear phagocytes (MP; monocytes, macrophages, microglia, and dendritic cells). Within the CNS, productive viral infection is found exclusively in microglia and meningeal, perivascular, and choroidal macrophages. MPs serve as the principal viral CNS reservoir. Animal models have been developed to recapitulate natural human HIV-1 infection. These include nonhuman primates, humanized mice, EcoHIV, and transgenic rodent models. These models have been used to study disease pathobiology, antiretroviral and immune modulatory agents, viral reservoirs, and eradication strategies. However, each of these models are limited to specific component(s) of human disease. Indeed, HIV-1 species specificity must drive therapeutic and cure studies. These have been studied in several model systems reflective of latent infections, specifically in MP (myeloid, monocyte, macrophages, microglia, and histiocyte cell) populations. Therefore, additional small animal models that allow productive viral replication to enable viral carriage into the brain and the virus-susceptible MPs are needed. To this end, this review serves to outline animal models currently available to study myeloid brain reservoirs and highlight areas that are lacking and require future research to more effectively study disease-specific events that could be useful for viral eradication studies both in and outside the CNS.
AB - The HIV-1 often evades a robust antiretroviral-mediated immune response, leading to persistent infection within anatomically privileged sites including the CNS. Continuous low-level infection occurs in the presence of effective antiretroviral therapy (ART) in CD4+ T cells and mononuclear phagocytes (MP; monocytes, macrophages, microglia, and dendritic cells). Within the CNS, productive viral infection is found exclusively in microglia and meningeal, perivascular, and choroidal macrophages. MPs serve as the principal viral CNS reservoir. Animal models have been developed to recapitulate natural human HIV-1 infection. These include nonhuman primates, humanized mice, EcoHIV, and transgenic rodent models. These models have been used to study disease pathobiology, antiretroviral and immune modulatory agents, viral reservoirs, and eradication strategies. However, each of these models are limited to specific component(s) of human disease. Indeed, HIV-1 species specificity must drive therapeutic and cure studies. These have been studied in several model systems reflective of latent infections, specifically in MP (myeloid, monocyte, macrophages, microglia, and histiocyte cell) populations. Therefore, additional small animal models that allow productive viral replication to enable viral carriage into the brain and the virus-susceptible MPs are needed. To this end, this review serves to outline animal models currently available to study myeloid brain reservoirs and highlight areas that are lacking and require future research to more effectively study disease-specific events that could be useful for viral eradication studies both in and outside the CNS.
KW - CNS
KW - HIV-1
KW - animal models
KW - brain
KW - humanized mice
KW - myeloid reservoir
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U2 - 10.1002/JLB.5VMR0322-161R
DO - 10.1002/JLB.5VMR0322-161R
M3 - Article
C2 - 36044375
AN - SCOPUS:85137227724
SN - 0741-5400
VL - 112
SP - 1285
EP - 1295
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 5
ER -