TY - JOUR
T1 - A novel simian immunodeficiency virus model that provides insight into mechanisms of human immunodeficiency virus central nervous system disease
AU - Zink, M. Christine
AU - Clements, Janice E.
PY - 2002
Y1 - 2002
N2 - Although highly active antiretroviral therapy (HAART) has reduced the incidence of dementia, a significant proportion of HIV-infected individuals cease therapy because of unacceptable side effects. Further, HAART is not available to the majority of HIV-infected people worldwide. Thus, animal models remain an important means by which to investigate the pathogenesis of HIV-induced CNS disease, particularly events during acute infection. We have developed an accelerated, consistent SIV/macaque model of HIV infection in which over 90 percent of inoculated macaques develop SIV encephalitis and behavioral changes by three months post-inoculation (p.i.). Viral load in the CSF during terminal infection and the ratio of MCP-1 in CSF:plasma are strong predictors of the severity of encephalitis at necropsy. The high incidence of CNS disease in this model provides an opportunity to correlate host and viral events in the CNS during acute infection with the later development of CNS disease. Using this model, we have demonstrated that viral DNA persists in the brain throughout asymptomatic infection despite significant suppression of active virus replication. We have further demonstrated that encephalitis is associated with the selective replication of macrophage-tropic, neurovirulent viral strains, and that recrudescence of virus replication during terminal infection occurs by reactivation of preexisting viral strains in the brain.
AB - Although highly active antiretroviral therapy (HAART) has reduced the incidence of dementia, a significant proportion of HIV-infected individuals cease therapy because of unacceptable side effects. Further, HAART is not available to the majority of HIV-infected people worldwide. Thus, animal models remain an important means by which to investigate the pathogenesis of HIV-induced CNS disease, particularly events during acute infection. We have developed an accelerated, consistent SIV/macaque model of HIV infection in which over 90 percent of inoculated macaques develop SIV encephalitis and behavioral changes by three months post-inoculation (p.i.). Viral load in the CSF during terminal infection and the ratio of MCP-1 in CSF:plasma are strong predictors of the severity of encephalitis at necropsy. The high incidence of CNS disease in this model provides an opportunity to correlate host and viral events in the CNS during acute infection with the later development of CNS disease. Using this model, we have demonstrated that viral DNA persists in the brain throughout asymptomatic infection despite significant suppression of active virus replication. We have further demonstrated that encephalitis is associated with the selective replication of macrophage-tropic, neurovirulent viral strains, and that recrudescence of virus replication during terminal infection occurs by reactivation of preexisting viral strains in the brain.
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U2 - 10.1080/13550280290101076
DO - 10.1080/13550280290101076
M3 - Review article
C2 - 12491150
AN - SCOPUS:0036947971
SN - 1355-0284
VL - 8
SP - 42
EP - 48
JO - Journal of neurovirology
JF - Journal of neurovirology
IS - SUPPL. 2
ER -