Changes in codon-pair bias of human immunodeficiency virus type 1 have profound effects on virus replication in cell culture.

ABSTRACT:

Background

Human immunodeficiency virus type 1 (HIV-1) has a biased nucleotide composition different from human genes. This raises the question of how evolution has chosen the nucleotide sequence of HIV-1 that is observed today, or to what extent the actual encoding contributes to virus replication capacity, evolvability and pathogenesis. Here, we applied the previously described synthetic attenuated virus engineering (SAVE) approach to HIV-1.

Results

Using synonymous codon pairs, we rationally recoded and codon pair-optimized and deoptimized different moieties of the HIV-1 gag and pol genes. Deoptimized viruses had significantly lower viral replication capacity in MT-4 and peripheral blood mononuclear cells (PBMCs). Varying degrees of ex vivo attenuation were obtained, depe

SUBMITTER: Martrus G 

PROVIDER: S-EPMC3726367 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature