Primary T-lymphocytes rescue the replication of HIV-1 DIS RNA mutants in part by facilitating reverse transcription
Open Access
- 23 January 2008
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 36 (5), 1578-1588
- https://doi.org/10.1093/nar/gkm1149
Abstract
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.Keywords
This publication has 90 references indexed in Scilit:
- Minimal Region Sufficient for Genome Dimerization in the Human Immunodeficiency Virus Type 1 Virion and Its Potential Roles in the Early Stages of Viral ReplicationJournal of Virology, 2007
- Dimer Initiation Signal of Human Immunodeficiency Virus Type 1: Its Role in Partner Selection during RNA Copackaging and Its Effects on RecombinationJournal of Virology, 2007
- HIV controls the selective packaging of genomic, spliced viral and cellular RNAs into virions through different mechanismsNucleic Acids Research, 2007
- Dimerization of retroviral RNA genomes: an inseparable pairNature Reviews Microbiology, 2004
- The cytoplasmic body component TRIM5α restricts HIV-1 infection in Old World monkeysNature, 2004
- Dimerization and Template Switching in the 5′ Untranslated Region between Various Subtypes of Human Immunodeficiency Virus Type 1Journal of Virology, 2003
- Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif proteinNature, 2002
- Non–coding RNA genes and the modern RNA worldNature Reviews Genetics, 2001
- Initial sequencing and analysis of the human genomeNature, 2001
- Evidence that a Kissing Loop Structure Facilitates Genomic RNA Dimerisation in HIV-1Journal of Molecular Biology, 1996