TY - JOUR
T1 - In vivo characterization of macrophage-tropic simian immunodeficiency virus molecular clones in rhesus macaques
AU - Gumber, Sanjeev
AU - Amancha, Praveen Kumar
AU - Yen, Po Jen
AU - Villinger, Francois
AU - Gabuzda, Dana
AU - Byrareddy, Siddappa N.
N1 - Publisher Copyright:
© 2018, Journal of NeuroVirology, Inc.
PY - 2018/8/1
Y1 - 2018/8/1
N2 - Macrophages are a major target of HIV/SIV infection and play an important role in pathogenesis by serving as viral reservoirs in the central nervous system. Previously, a unique early SIVmac251 envelope (Env) variant, deSIV147 was cloned from blood of a rhesus macaque with rapid disease progression and SIV-associated encephalitis. Here, we show that infectious molecular clone deSIV147 caused systemic infection in rhesus macaques following intravenous or intrarectal exposure. Next, we inoculated deSIV147 into macaques depleted of CD4+ T cells and found that animals were SIV-positive, with high plasma and CSF viral loads. These macaques also showed SIVp17-positive macrophages in brain, lymph nodes, colon, lung, and liver. Furthermore, accumulation of perivascular macrophages, multinucleated giant cells, and microgliosis was detected. These findings suggest that the neurotropic deSIV147 clone will be useful to study macrophage infection in HIV/SIV-associated neurocognitive disorders, gain insights into myeloid cell reservoirs in brain and other anatomical sites, as well as test strategies for eradication.
AB - Macrophages are a major target of HIV/SIV infection and play an important role in pathogenesis by serving as viral reservoirs in the central nervous system. Previously, a unique early SIVmac251 envelope (Env) variant, deSIV147 was cloned from blood of a rhesus macaque with rapid disease progression and SIV-associated encephalitis. Here, we show that infectious molecular clone deSIV147 caused systemic infection in rhesus macaques following intravenous or intrarectal exposure. Next, we inoculated deSIV147 into macaques depleted of CD4+ T cells and found that animals were SIV-positive, with high plasma and CSF viral loads. These macaques also showed SIVp17-positive macrophages in brain, lymph nodes, colon, lung, and liver. Furthermore, accumulation of perivascular macrophages, multinucleated giant cells, and microgliosis was detected. These findings suggest that the neurotropic deSIV147 clone will be useful to study macrophage infection in HIV/SIV-associated neurocognitive disorders, gain insights into myeloid cell reservoirs in brain and other anatomical sites, as well as test strategies for eradication.
KW - Central nerveous system
KW - Macrophage-tropic
KW - Macrophages
KW - Myeloid cells
KW - Rhesus macaques
KW - SIV
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U2 - 10.1007/s13365-018-0628-2
DO - 10.1007/s13365-018-0628-2
M3 - Article
C2 - 29594984
AN - SCOPUS:85045050741
SN - 1355-0284
VL - 24
SP - 411
EP - 419
JO - Journal of neurovirology
JF - Journal of neurovirology
IS - 4
ER -