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14:23
A Restriction Enzyme Based Cloning Method to Assess the In vitro Replication Capacity of HIV-1 Subtype C Gag-MJ4 Chimeric Viruses
Published on: August 31, 2014
Significant changes in integrase-associated HIV-1 replication capacity between early and late isolates
Elena Capel1, Mariona Parera, Bonaventura Clotet
1Fundació irsiCaixa, Hospital Universitari Germans Trias i Pujol, Badalona 08916, Spain.
Virology
|July 25, 2013
Summary
Genetic diversification in human immunodeficiency virus type 1 (HIV-1) integrase impacts viral replication. Late HIV-1 isolates show reduced replication capacity, linked to specific integrase genetic changes.
Area of Science:
- Virology
- Molecular Biology
- Genetics
Background:
- The human immunodeficiency virus type 1 (HIV-1) pandemic is characterized by continuous, extensive genetic diversification.
- The role of viral genetic changes, particularly in the integrase enzyme, on viral replication capacity (RC) requires further investigation.
Purpose of the Study:
- To investigate the effect of HIV-1 subtype B integrase sequence diversification on ex vivo viral replication capacity.
- To compare the integrase sequences and associated RC of early and late HIV-1 isolates.
Main Methods:
- Amplification and recombination of 94 HIV-1 subtype B integrase sequences from antiretroviral-naive viruses (isolated 15 years apart) with an HIV-1 infectious clone.
- Determination of viral replication capacity (RC) using a T cell line infected with reporter viruses expressing green fluorescent protein.
- Analysis of integrase sequence conservation and identification of specific amino acid polymorphisms.
Main Results:
- Significant differences in integrase-mediated RC were observed between recombinant viruses from early and late isolates (p=0.0286).
- Integrases from late isolates exhibited significantly lower sequence conservation scores compared to an ancestral subtype B sequence (p<0.0001).
- Specific integrase amino acid polymorphisms (S17N, I72V, S119P, D256E) were associated with reduced ex vivo viral RC.
Conclusions:
- HIV-1 integrase sequence diversification has demonstrably affected ex vivo viral replication capacity.
- Specific genetic variations within the HIV-1 integrase enzyme are linked to altered viral fitness.
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