Editing of HIV-1 RNA by the double-stranded RNA deaminase ADAR1 stimulates viral infection.
Adenosine deaminases that act on dsRNA (ADARs) are enzymes that target double-stranded regions of RNA converting adenosines into inosines (A-to-I editing) thus contributing to genome complexity and fine regulation of gene expression. It has been described that a member of the ADAR family, ADAR1, can target viruses and affect their replication process. Here we report evidence showing that ADAR1 stimulates human immuno deficiency virus type 1 (HIV-1) replication by using both editing-dependent and editing-independent mechanisms. We show that over-expression of ADAR1 in HIV-1 producer cells increases viral protein accumulation in an editing-independent manner. Moreover, HIV-1 virions generated in the presence of over-expressed ADAR1 but not an editing-inactive ADAR1 mutant are released more efficiently and display enhanced infectivity, as demonstrated by challenge assays performed with T cell lines and primary CD4(+) T lymphocytes. Finally, we report that ADAR1 associates with HIV-1 RNAs and edits adenosines in the 5' untranslated region (UTR) and the Rev and Tat coding sequence. Overall these results suggest that HIV-1 has evolved mechanisms to take advantage of specific RNA editing activity of the host cell and disclose a stimulatory function of ADAR1 in the spread of HIV-1.
Doria
Margherita
M
Laboratory of Immunoinfectivology, Children's Hospital Bambino Gesù, 00165, Rome, Italy. doria@uniroma2.it
Neri
Francesca
F
Gallo
Angela
A
Farace
Maria Giulia
MG
Michienzi
Alessandro
A
D000243:Adenosine Deaminase / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology; D002460:Cell Line; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D054298:Human Immunodeficiency Virus Proteins / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D017393:RNA Editing; D012367:RNA, Viral / Q000378:metabolism*; D016601:RNA-Binding Proteins; D014771:Virion / Q000378:metabolism
D054298:Human Immunodeficiency Virus Proteins; D012367:RNA, Viral; D016601:RNA-Binding Proteins; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase