HIV-1 replication and APOBEC3 antiviral activity are not regulated by P bodies.
The APOBEC3 cytidine deaminases play a critical role in host-mediated defense against exogenous viruses, most notably, human immunodeficiency virus type-1 (HIV-1) and endogenous transposable elements. APOBEC3G and APOBEC3F interact with numerous proteins that regulate cellular RNA metabolism, including components of the RNA-induced silencing complex (RISC), and colocalize with a subset of these proteins to mRNA processing bodies (P bodies), which are sites of mRNA translational repression and decay. We sought to determine the role of P bodies and associated proteins in HIV-1 replication and APOBEC3 antiviral activity. While we established a positive correlation between APOBEC3 protein incorporation into virions and localization to P bodies, depletion of the P-body components DDX6 or Lsm1 did not affect HIV-1 replication, APOBEC3 packaging into virions or APOBEC3 protein mediated inhibition of HIV-1 infectivity. In addition, neither HIV-1 genomic RNA nor Gag colocalized with P-body proteins. However, simultaneous depletion of multiple Argonaute family members, the effector proteins of RISC, could modestly increase viral infectivity. Because some APOBEC3 proteins interact with several Argonaute proteins, we also tested whether they could modulate microRNA (miRNA) activity. We found no evidence for the specific regulation of miRNA function by the APOBEC3 proteins, though more general effects on transfected gene expression were observed. In sum, our results indicate that P bodies and certain associated proteins do not regulate HIV-1 replication or APOBEC3 protein antiviral activity. Localization to P bodies may therefore provide a means of sequestering APOBEC3 enzymatic activity away from cellular DNA or may be linked to as yet unidentified cellular functions.
Department of Infectious Diseases, Kings College London School of Medicine, Guy's Hospital, London, United Kingdom.
Prabhjeet K
PK
Phalora
Nathan M
NM
Sherer
Steven M
SM
Wolinsky
Chad M
CM
Swanson
Michael H
MH
Malim
D000071478:APOBEC Deaminases; D002460:Cell Line; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000276:immunology* / Q000378:metabolism*; D053487:DEAD-box RNA Helicases / Q000172:deficiency / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000378:metabolism; D020871:RNA Stability; D016601:RNA-Binding Proteins / Q000378:metabolism; D014779:Virus Replication
C464824:LSM1 protein, human; D011518:Proto-Oncogene Proteins; D016601:RNA-Binding Proteins; D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; D003564:Cytidine Deaminase; C094683:DDX6 protein, human; D053487:DEAD-box RNA Helicases