The central nervous system as a reservoir for simian immunodeficiency virus (SIV): steady-state levels of SIV DNA in brain from acute through asymptomatic infection.
Latent reservoirs of human immunodeficiency virus (HIV) present significant challenges for eradicating HIV from infected persons, particularly reservoirs in the brain established during acute infection. A simian immunodeficiency virus (SIV)/macaque model of HIV dementia was used to show that viral DNA levels in the brain remained at constant levels from acute through asymptomatic infection, despite significant down-regulation of viral RNA in the brain after the acute phase of infection. Viral replication in the brain coincided with activation of macrophages and microglia in the central nervous system; down-regulation of viral replication coincided with increased infiltration of cytotoxic lymphocytes and reduced activation of macrophages and microglia in the brain. Comparison of viral genotypes in the central nervous system and peripheral blood mononuclear cells suggests that recrudescence of viral replication in brain occurs by reactivation of latent viral DNA. Latent virus in the brain must be considered in therapeutic strategies to eliminate HIV from infected persons.
Clements
Janice E
JE
Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. jclement@jhmi.edu
Babas
Tahar
T
Mankowski
Joseph L
JL
Suryanarayana
K
K
Piatak
Michael
M
Tarwater
Patrick M
PM
Lifson
Jeffrey D
JD
Zink
M Christine
MC
D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001921:Brain / Q000276:immunology / Q000821:virology*; D002353:Carrier State / Q000097:blood / Q000134:cerebrospinal fluid / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D004195:Disease Models, Animal; D005838:Genotype; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D008254:Macaca nemestrina; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology; D008565:Membrane Proteins / Q000032:analysis; D017628:Microglia / Q000276:immunology; D011506:Proteins; D012367:RNA, Viral / Q000032:analysis; D016601:RNA-Binding Proteins / Q000032:analysis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000134:cerebrospinal fluid / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000302:isolation & purification / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019562:Viral Load; D017735:Virus Latency; D014779:Virus Replication; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D004279:DNA, Viral; D000949:Histocompatibility Antigens Class II; D008565:Membrane Proteins; D011506:Proteins; D012367:RNA, Viral; D016601:RNA-Binding Proteins; C067980:CD68 antigen, human; D000097382:CD68 Molecule