Neuropathogenesis of simian immunodeficiency virus in neonatal rhesus macaques.
Neonatal human immunodeficiency virus (HIV) infection usually occurs intrapartum or postpartum and results in a higher incidence of neurological dysfunction than is seen in adults. To explore the neuropathogenesis of neonatal HIV infection, we infected neonatal macaques with simian immunodeficiency virus (SIV) and followed the course of infection focusing on early time points. Infected neonates had decreased brain growth and mild histological changes in brain that resembled those seen in pediatric AIDS, including perivascular infiltrates of mononuclear cells, mineralization of vessels in the basal ganglia, and gliosis. The perivascular lesions and gliosis were associated with the presence of occasional infected cells that required in situ hybridization with radiolabeled riboprobes for detection. Using this technique, SIV-infected cells were detected in the brain parenchyma within 7 days of infection. These findings were confirmed by nested PCR for SIVgag DNA in brain and RT-PCR for viral RNA in cerebrospinal fluid. Together, these techniques revealed SIV infection of the CNS in 12 of 13 neonates infected with SIVmac239, 3 of 3 infected with SIVmac251, and 2 of 2 infected with SIVmac239/316. The prevalence of CNS infection was indistinguishable from that of older animals infected with the same dose and stock of virus, but neonates appeared to have fewer infected cells in the CNS and detecting them required more sensitive techniques. This observation was true regardless of inoculum and despite the fact that neonates had equal or greater viral loads in the periphery compared with older animals. These data suggest that maturation-dependent host factors have a major impact on the neuropathogenesis of pediatric AIDS.
Westmoreland
S V
SV
Division of Comparative Pathology, New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts, USA.
Williams
K C
KC
Simon
M A
MA
Bahn
M E
ME
Rullkoetter
A E
AE
Elliott
M W
MW
deBakker
C D
CD
Knight
H L
HL
Lackner
A A
AA
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000254:growth & development / Q000378:metabolism / Q000473:pathology / Q000821:virology; D002494:Central Nervous System Infections / Q000134:cerebrospinal fluid / Q000473:pathology* / Q000821:virology; D018450:Disease Progression; D015683:Gene Products, gag / Q000134:cerebrospinal fluid / Q000378:metabolism; D017403:In Situ Hybridization; D008253:Macaca mulatta; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D009929:Organ Size; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000096:biosynthesis / Q000134:cerebrospinal fluid; D016097:Simian Acquired Immunodeficiency Syndrome / Q000134:cerebrospinal fluid / Q000473:pathology* / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity*; D013997:Time Factors; D019562:Viral Load; D014779:Virus Replication
C066594:Gag protein p27, Simian immunodeficiency virus; D015683:Gene Products, gag; D012367:RNA, Viral