Primary T-lymphocytes rescue the replication of HIV-1 DIS RNA mutants in part by facilitating reverse transcription.
The dimerization initiation site (DIS) stem-loop within the HIV-1 RNA genome is vital for the production of infectious virions in T-cell lines but not in primary cells. In comparison to peripheral blood mononuclear cells (PBMCs), which can support the replication of both wild type and HIV-1 DIS RNA mutants, we have found that DIS RNA mutants are up to 100 000-fold less infectious than wild-type HIV-1 in T-cell lines. We have also found that the cell-type-dependent replication of HIV-1 DIS RNA mutants is largely producer cell-dependent, with mutants displaying a greater defect in viral cDNA synthesis when viruses were not derived from PBMCs. While many examples exist of host-pathogen interplays that are mediated via proteins, analogous examples which rely on nucleic acid triggers are limited. Our data provide evidence to illustrate that primary T-lymphocytes rescue, in part, the replication of HIV-1 DIS RNA mutants through mediating the reverse transcription process in a cell-type-dependent manner. Our data also suggest the presence of a host cell factor that acts within the virus producer cells. In addition to providing an example of an RNA-mediated cell-type-dependent block to viral replication, our data also provides evidence which help to resolve the dilemma of how HIV-1 genomes with mismatched DIS sequences can recombine to generate chimeric viral RNA genomes.
Jones
Kate L
KL
Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Australia.
Sonza
Secondo
S
Mak
Johnson
J
D020121:5' Untranslated Regions / Q000737:chemistry; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000096:biosynthesis; D019281:Dimerization; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008264:Macrophages / Q000821:virology; D008969:Molecular Sequence Data; D009154:Mutation; D012367:RNA, Viral / Q000737:chemistry*; D048348:Reverse Transcription; D013601:T-Lymphocytes / Q000821:virology*; D014779:Virus Replication
D020121:5' Untranslated Regions; D018076:DNA, Complementary; D012367:RNA, Viral