HIV Type 1 That Select tRNA His or tRNA Lys1,2 as Primers for Reverse Transcription Exhibit Different Infectivities in Peripheral Blood Mononuclear Cells

Abstract

The replication in human peripheral blood mononuclear cells (PBMC) of unique HIV-1 that select tRNA^His or tRNA^Lys1,2 for reverse transcription was compared to the wild-type virus that uses tRNA^Lys,3. HIV-1 with only the primer-binding site (PBS) changed to be complementary to these alternative tRNAs initially replicated more slowly than the wild-type virus in PBMC, although all viruses eventually reached equivalent growth as measured by p24 antigen. Viruses with only a PBS complementary to the 3′ terminal 18 nucleotides of tRNA^His or tRNA^Lys1,2 reverted to use tRNA^Lys3. HIV-1 with mutations in the U5-PBS to allow selection of tRNA^His and tRNA^Lys1,2 following long-term growth in SupT1 cells were also evaluated for growth and PBS stability following replication in PBMC. Although both viruses initially grew slower than wild type, they maintained a PBS complementary to the starting tRNA and did not revert to the wild-type PBS after long-term culture in PBMC. Analysis of the U5-PBS regions following long-term culture in PBMC also revealed few changes from the starting sequences. The virus that stably used tRNA^His was less infectious than the wild type. In contrast, the virus that stably used tRNA^Lys1,2 evolved to be as infectious as wild-type virus following extended culture in PBMC. The results of these studies highlight the impact of the host cell on the tRNA primer selection process and subsequent infectivity of HIV-1.