HIV in central nervous system and behavioral development: an HIV-2287 macaque model of AIDS.
OBJECTIVE
To determine which route of inoculation produced consistent and frequent HIV infection in the central nervous system (CNS) and alterations in cognitive and motor development in infant macaques.


METHODS
Infant macaques (Macaca nemestrina) were inoculated with the highly pathogenic strain HIV-2287 intravenously (n = 3) or intrathecally (n = 3). Uninfected infants were evaluated as controls. Disease progression was evaluated by virological assessment of blood and cerebral spinal fluid (CSF), CD4 T cell count in blood, and quinolinic acid levels in CSF (a surrogate marker of neuronal cell damage). The effect of HIV infection on cognitive and motor development in infants was monitored during the 6-month study.


RESULTS
Either route of HIV-2287 inoculation produced detectable viral RNA in CSF and productive infection in blood. Detection of virus in CSF paralleled a rise in quinolinic acid levels. All HIV-infected infants experienced a severe and rapid decline in CD4 T cell counts by 10 weeks after viral infection. HIV-infected infants, particularly those infected by the intravenous route, exhibited delays in reaching cognitive and motor milestones, which paralleled neuropathological changes.


CONCLUSIONS
The HIV-2287 infant model produced a high incidence of viral infection in the CNS regardless of the route of inoculation. Significant alteration in neurobehavioral development was observed in HIV-infected infants, and this measure was significantly impaired particularly in infants infected by the intravenous route. These data, coupled with the ability to detect viral RNA and changes in quinolinic acid levels in CSF, may allow quantitative evaluation of drug and immune candidates for treating neurological effects of AIDS.
Kinman
Loren M
LM
Department of Pharmaceutics and Washington National Primate Research Center, University of Washington, Seattle Washington 98195-7610, USA.
Worlein
Julie M
JM
Leigh
Jennifer
J
Bielefeldt-Ohmann
Helle
H
Anderson
David M
DM
Hu
Shiu-Lok
SL
Morton
William R
WR
Anderson
Bradley D
BD
Ho
Rodney J Y
RJ
D015526:AIDS Dementia Complex / Q000134:cerebrospinal fluid / Q000473:pathology / Q000821:virology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D003071:Cognition; D018450:Disease Progression; D015498:HIV-2; D008254:Macaca nemestrina; D023421:Models, Animal; D009048:Motor Skills; D017378:Quinolinic Acid / Q000134:cerebrospinal fluid; D012367:RNA, Viral / Q000134:cerebrospinal fluid
D012367:RNA, Viral; D017378:Quinolinic Acid