Sequence and Functional Variation in the HIV-1 Rev Regulatory Axis
| Autor: | Patrick E. H. Jackson, Godfrey Dzhivhuho, Marie-Louise Hammarskjold, David Rekosh |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Viral protein
viruses Response element HIV Infections Biology Virus Replication medicine.disease_cause Genes env Article Nucleic acid secondary structure 03 medical and health sciences Immune system Virology medicine Humans Cytotoxic T cell 030304 developmental biology 0303 health sciences 030302 biochemistry & molecular biology Genetic Variation rev Gene Products Human Immunodeficiency Virus Cell biology Alternative Splicing Infectious Diseases HIV Rev response element Ribonucleoproteins Ran RNA splicing HIV-1 RNA Viral |
| Zdroj: | Curr HIV Res |
| ISSN: | 1570-162X |
| DOI: | 10.2174/1570162x18666200106112842 |
| Popis: | Background: To complete its replication cycle, HIV-1 requires the nucleocytoplasmic export of intron-containing viral mRNAs. This process is ordinarily restricted by the cell, but HIV overcomes the block by means of a viral protein, Rev, and an RNA secondary structure found in all unspliced and incompletely spliced viral mRNAs called the Rev Response Element (RRE). In vivo activity of the Rev-RRE axis requires Rev binding to the RRE, oligomerization of Rev to form a competent ribonucleoprotein complex, and recruitment of cellular factors including Crm1 and RanGTP in order to export the targeted transcript. Sequence variability is observed among primary isolates in both Rev and the RRE, and the activity of both can be modulated through relatively small sequence changes. Primary isolates show differences in Rev-RRE activity and a few studies have found a correlation between lower Rev-RRE activity and slower progression of clinical disease. Lower Rev-RRE activity has also been associated with the evasion of cytotoxic T lymphocyte mediated killing. Conclusions: The HIV-1 Rev-RRE regulatory axis is an understudied mechanism by which viral adaptation to diverse immune milieus may take place. There is evidence that this adaptation plays a role in HIV pathogenesis, particularly in immune evasion and latency, but further studies with larger sample sizes are warranted. |
| Databáze: | OpenAIRE |
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