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Simian immunodeficiency virus encephalitis in rhesus macaques is associated with rapid disease progression
S V Westmoreland1, E Halpern, A A Lackner
1New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772, USA.
Abstract:
Central nervous system (CNS) disease is a major feature of simian immunodeficiency virus (SIV) infection of macaques. To define the spectrum of CNS lesions in SIV-infected macaques and the potential associations with viral strain and disease course, we performed a retrospective analysis of necropsies on 124 macaques with SIV-induced AIDS. Histologic evidence of CNS disease was observed in 71 (57.3%) of the 124 animals. SIV encephalitis was the most common CNS lesion occurring in 43.7% (31/71) of the animals with CNS disease and 25% of all animals. The incidence of SIVE correlated significantly with shortened survival (P=0.0207). In addition, SIVE was seen in 42.9% (15/35) of rapid progressors (animals that died within 200 days) compared to only 18% (16/89) of normal progressors (animals that lived longer than 200 days) (P=0.011). Animals with SIVE had higher viral loads in peripheral blood than those that did not, but this difference did not reach statistical significance. Similarly, while animals infected with uncloned SIVmac251 had a higher incidence of SIVE (27.5%; 14/51) than animals infected with molecularly cloned SIVmac239 and its T-cell tropic derivatives (18.5%; 10/54) this difference was not statistically significant. In this study rapid disease progression and SIVE were highly correlated making separation of viral determinants of virulence from those of neurovirulence difficult.
Insights
Central nervous system (CNS) disease is common in simian immunodeficiency virus (SIV) infection. SIV encephalitis (SIVE) strongly correlates with rapid disease progression and shorter survival in macaques.
Area of Science:
- Veterinary Neurology
- Immunovirology
- Primate Models
Background:
- Central nervous system (CNS) disease is a significant complication of simian immunodeficiency virus (SIV) infection in macaques.
- Understanding the range of CNS lesions and their links to viral factors and disease progression is crucial.
Purpose of the Study:
- To characterize CNS lesions in SIV-infected macaques.
- To investigate associations between CNS lesions, viral strains, and disease course.
Main Methods:
- Retrospective analysis of necropsy data from 124 SIV-infected macaques.
- Histopathological examination to identify CNS lesions, particularly SIV encephalitis (SIVE).
- Correlation analysis with survival time, disease progression rate, and viral characteristics.
Main Results:
- CNS disease was observed in 57.3% of macaques.
- SIV encephalitis (SIVE) was the most frequent CNS lesion (25% of all animals).
- SIVE incidence significantly correlated with shortened survival (P=0.0207) and rapid disease progression (P=0.011).
Conclusions:
- SIV encephalitis is a common and significant CNS lesion in SIV-infected macaques.
- Rapid disease progression and SIVE are highly correlated, complicating the identification of specific viral determinants for virulence and neurovirulence.