Evolution of SIV envelope in morphine-dependent rhesus macaques with rapid disease progression
1Laboratory of Viral Immunology, Departments of Microbiology, Ponce School of Medicine, Ponce, Puerto Rico 00732.
Abstract:
Three morphine-dependent rhesus macaques that developed accelerated AIDS after virus inoculation, along with three control macaques, were followed for evolution of the SIV/17E-Fr envelope. Viral RNA was isolated from plasma samples collected at weeks 6, 12, and 20 postinfection. A 482-nucleotide fragment in the viral env was amplified and cloned into a pCR2.1-TOPO vector. Between 5 and 10 clones were sequenced at each time point from individual monkeys. The sequence analysis showed more mutations in the control animals compared to those seen in the morphine-dependent animals. The virus at different points did not separate completely in phylogenetic analysis. However, the phylogenetic clustering was more apparent in the control animals. Viral diversity and divergence were significantly higher in the control animals. The control animals lost N-glycosylation sites more rapidly. These results suggest that morphine dependence diminished virus evolution in SHIV/SIV-infected rhesus macaques and there was an inverse correlation between virus evolution and onset of clinical disease.
Insights
Morphine dependence in rhesus macaques slowed simian-human immunodeficiency virus (SHIV) evolution. This reduced viral diversity and divergence, correlating with a faster onset of acquired immunodeficiency syndrome (AIDS).
Area of Science:
- Virology
- Immunology
- Primatology
Background:
- Morphine dependence is known to affect immune function.
- The impact of morphine on simian immunodeficiency virus (SIV) evolution and disease progression in macaques is not fully understood.
Purpose of the Study:
- To investigate the effect of morphine dependence on the evolution of the SIV/17E-Fr envelope in rhesus macaques.
- To determine the correlation between virus evolution and the onset of acquired immunodeficiency syndrome (AIDS).
Main Methods:
- Three morphine-dependent and three control rhesus macaques were inoculated with SIV/17E-Fr.
- Viral RNA was isolated from plasma at 6, 12, and 20 weeks postinfection.
- A fragment of the viral env gene was amplified, cloned, and sequenced.
Main Results:
- Sequence analysis revealed fewer mutations in morphine-dependent macaques compared to controls.
- Viral diversity and divergence were significantly higher in control animals.
- Control animals showed more apparent phylogenetic clustering and faster loss of N-glycosylation sites.
Conclusions:
- Morphine dependence diminished virus evolution in SHIV/SIV-infected rhesus macaques.
- An inverse correlation exists between virus evolution and the onset of clinical disease (AIDS).
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