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Suboptimal nucleotides in the infectious, pathogenic simian immunodeficiency virus clone SIVmac239
L Alexander1, L Denekamp, S Czajak
1Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Journal of Virology
|March 27, 2001
Summary
Researchers studied simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV) in monkeys. Key genetic changes occurred in infected animals, suggesting the original virus strains were not optimally adapted for persistent infection.
Area of Science:
- Virology
- Genetics
- Immunology
Background:
- Persistent high viral loads are characteristic of lentiviral infections.
- Understanding viral evolution in vivo is crucial for developing effective treatments.
Purpose of the Study:
- To investigate sequence changes in simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV) in infected non-human primates.
- To identify specific genetic loci that undergo consistent mutations during persistent infection.
Main Methods:
- Analysis of viral sequences from four monkeys with high, persistent viral loads (two infected with SIVmac239, two with SHIVnef).
- Comparison of viral sequences from infected animals with in vitro cultured cells.
Main Results:
- Consistent nucleotide changes were observed at four specific loci in all infected animals.
- These mutations occurred in the 5' long terminal repeat, pol gene, and overlapping rev/env gene regions.
- The observed mutations represent consensus sequences for primate lentiviruses and were not present in the initial inoculum or in vitro cultures.
Conclusions:
- The cloned SIVmac239, while pathogenic, is not optimally adapted at these four nucleotide positions for sustained high viral replication.
- In vivo evolution leads to sequence changes that are consensus for primate lentiviruses, indicating adaptation during persistent infection.