Pathogenesis of lymphocyte-tropic and macrophage-tropic SIVmac infection in the brain.
J Neurovirol
; 1(1): 78-91, 1995 Mar.
Article
em En
| MEDLINE
| ID: mdl-9222344
ABSTRACT
SIVmac239 replicates productivity in activated CD4+ T lymphocytes, but inefficiently in macrophages from rhesus macrophages. Inoculation of the virus into animals results in an acute, highly productive burst of virus replication in activated T lymphocytes in lymphoid tissues and infected cells invade the central nervous system (CNS). This phase lasts a few weeks and is eventually followed by development of immunosuppression of different degrees of severity, opportunistic infections, and tumors related to the loss of T lymphocytes. On rare occasions, infected immunosuppressed animals develop encephalitis and/or interstitial pneumonia, syndromes that are associated with selection of mutant viruses that replicate efficiently in macrophages of these tissues. Usually, however, brains of animals dying with AIDS caused by SIVmac239 appear histologically normal. Is the brain infected with virus? We report here on a macaque dying with AIDS, a neuroinvasive tumor and interstitial pneumonia associated with macrophage-tropic virus. Except for focal infiltration of tumor cells, the brain was normal histologically. We examined the virus and viral DNA from different tissues and found that lymphocytes but not macrophages from lymph nodes and spleen yielded virus, whereas macrophages but not lymphocytes from the lung produced virus. No virus was recovered from the brain but small amounts of viral p27 were present in the brain homogenate. Viral sequences were present in the brain as determined by PCR from tissue DNA. Comparison showed that the viral sequences in the brain closely resembled those from the spleen. Presumably, the virus caused a minimally productive infection detectable by production of small amounts of p27, but was not accompanied by any histopathological changes. It is unclear why the macrophage-tropic virus in the lung failed to 'take-off' in the brain of this animal. To determine whether this virus had encephalitic potential, we inoculated the lung homogenate containing cell-free, macrophage tropic virus into a young pigtail macaque, a species known to be sensitive to primate lentiviral infections. This animal developed severe encephalitis 10 weeks later. Virus from the brain was very similar to the inoculum virus, proving its encephalitic potential. Possible reasons for the differences in neurovirulence of this virus between the two animals remain speculative.
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
/
Linfócitos T
/
Vírus da Imunodeficiência Símia
/
Encefalite Viral
/
Macrófagos
Tipo de estudo:
Etiology_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Neurovirol
Assunto da revista:
NEUROLOGIA
/
VIROLOGIA
Ano de publicação:
1995
Tipo de documento:
Article
País de afiliação:
Estados Unidos