Dynamics of simian immunodeficiency virus populations in blood and cerebrospinal fluid over the full course of infection.
BACKGROUND. Human immunodeficiency virus (HIV) replication and compartmentalization in the central nervous system, including in cerebrospinal fluid (CSF), are associated with severe neurological disease and may contribute to viral persistence during antiretroviral therapy. To understand the relationships between viral populations in multiple compartments, we performed a systematic longitudinal characterization of viral populations in blood plasma and CSF obtained at short time intervals over the full course of infection in 3 macaques infected with simian immunodeficiency virus (SIVsm strain E660).


METHODS
Complex viral genetic populations in blood plasma and CSF were characterized using a heteroduplex tracking assay targeted to the V1/V2 hypervariable region of env. To identify signs of neurological disease, monocyte chemoattractant protein (MCP)-1 levels in CSF and CD68(+) monocyte/macrophage infiltration in brain tissues were quantified.


RESULTS
Two patterns of blood/CSF viral dynamics were apparent as infection progressed: concordant blood/CSF viral evolution and discordant blood/CSF viral evolution. Perivascular CD68(+) cells in autopsy brain tissue and elevated CSF MCP-1 levels accompanied blood/CSF viral population discordance but not concordance.


CONCLUSIONS
Two distinct patterns of blood/CSF viral population dynamics can be observed in SIV-infected macaques, and the patterns may be associated with different neurological disease outcomes.
Harrington
Patrick R
PR
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Connell
Mary J
MJ
Meeker
Rick B
RB
Johnson
Philip R
PR
Swanstrom
Ronald
R
D015526:AIDS Dementia Complex / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001921:Brain / Q000276:immunology / Q000821:virology; D002555:Cerebrospinal Fluid / Q000821:virology*; D018932:Chemokine CCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D019143:Evolution, Molecular; D005838:Genotype; D020180:Heteroduplex Analysis; D006801:Humans; D008253:Macaca mulatta; D008264:Macrophages / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D012367:RNA, Viral / Q000097:blood*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000145:classification / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D019562:Viral Load; D014779:Virus Replication; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018932:Chemokine CCL2; D012367:RNA, Viral; C067980:CD68 antigen, human; D000097382:CD68 Molecule