The genetic evolution of the envelope gene of simian immunodeficiency virus in cynomolgus macaques infected with a complex virus pool
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N Almond1, A Jenkins, A B Heath
1National Institute for Biological Standards and Control, Potters Bar, Herts, United Kingdom.
Abstract:
Two cynomolgus macaques were infected with a complex, but characterized, challenge stock of simian immunodeficiency virus (SIVmac251 32H). The polymerase chain reaction was applied in a temporal sequence analysis to determine the sequences of the gp120 region of the SIV env gene, which were present in the blood of both macaques at 1, 6, and 15 months postinfection (p.i.). At 1 month p.i. selected sequences, which had been present in the original virus challenge stock, were reisolated. At later times, new sequences emerged, which had not been detected in the original virus challenge stock. Changes in sequence were restricted to specific regions of gp120, notably those equivalent to V1, V2, V4, and V5 of HIV-1, but not V3. The diversity and the rate of appearance of new sequences in the V1 region suggest that genetic evolution occurs by mechanisms in addition to nucleotide substitutions. These results are discussed in relation to the role of the envelope protein in the generation of protective immunity against infection with immunodeficiency viruses.
Insights
New simian immunodeficiency virus (SIV) sequences emerged in macaques post-infection, indicating rapid viral evolution. Genetic changes in the SIV env gene suggest complex evolutionary mechanisms beyond simple mutations.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Simian immunodeficiency virus (SIV) is a non-human primate lentivirus.
- SIV infection in macaques serves as a model for studying human immunodeficiency virus (HIV) pathogenesis.
- The SIV env gene encodes the envelope glycoprotein (gp120), crucial for viral entry and immune evasion.
Purpose of the Study:
- To investigate the genetic evolution of SIV env gene sequences in vivo.
- To identify changes in viral quasispecies over time post-infection.
- To explore the relationship between viral evolution and the host immune response.
Main Methods:
- Infection of two cynomolgus macaques with SIVmac251.
- Temporal sequence analysis of the SIV env gp120 region using polymerase chain reaction (PCR) at 1, 6, and 15 months post-infection.
- Comparison of viral sequences with the original challenge stock.
Main Results:
- Viral sequences from the original challenge stock were reisolated at 1 month post-infection.
- Novel SIV env gp120 sequences, not present in the initial stock, emerged at later time points.
- Sequence changes were concentrated in specific gp120 regions (V1, V2, V4, V5), with notable diversity in the V1 region.
- The rate of new sequence appearance suggests evolutionary mechanisms beyond nucleotide substitution.
Conclusions:
- SIV undergoes rapid genetic evolution in vivo, generating new viral variants.
- The V1 region of the SIV env gene appears to be a major site of adaptive evolution.
- Understanding SIV evolution is critical for developing effective vaccines and therapies against immunodeficiency viruses.