A simian immunodeficiency virus macaque model of highly active antiretroviral treatment: viral latency in the periphery and the central nervous system.
OBJECTIVE
Here, simian immunodeficiency virus (SIV) macaque models are examined for their strengths in identifying in-vivo sites of HIV latency and persistent virus replication during highly active antiretroviral treatment (HAART). The best characterized HIV reservoir in HAART-treated persons is resting CD4 T cells in blood, although residual virus also comes from other reservoirs. Nonhuman primate/SIV models of HAART have been developed to characterize potential HIV reservoirs, particularly the central nervous system (CNS) and stem cells in bone marrow, known and potential reservoirs of latent virus that are difficult to study in humans.


RESULTS
Few SIV macaque models of HAART have examined plasma and cerebrospinal fluid virus decay, the number of resting CD4 T cells harboring replication-competent latent SIV, HAART-treatment effect on the CNS, or residual viral replication or viral DNA levels in that tissue. Using a consistent, accelerated SIV macaque model, we characterized peripheral viral reservoirs, including those in the CNS, among HAART-treated macaques. The SIV model reproduces latency in memory CD4 T cells throughout the body and indicates that the CNS contains a stable SIV DNA reservoir.


CONCLUSIONS
An SIV macaque model of HAART recapitulating viral latency, particularly in the CNS, is required to study therapeutic approaches for a functional HIV cure.
Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. jclements@jhmi.edu
Janice E
JE
Clements
Lucio
L
Gama
David R
DR
Graham
Joseph L
JL
Mankowski
M C
MC
Zink
D000818:Animals; D001853:Bone Marrow / Q000821:virology; D002490:Central Nervous System / Q000821:virology*; D004195:Disease Models, Animal; D006412:Hematopoietic Stem Cells / Q000821:virology; D006801:Humans; D008251:Macaca / Q000821:virology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity*; D017735:Virus Latency
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