Restriction of retroviral replication by APOBEC3G/F and TRIM5alpha.
Pathogenic viral infections have exerted selection pressure on their hosts to evolve cellular antiviral inhibitors referred to as restriction factors. Examples of such molecules are APOBEC3G, APOBEC3F and TRIM5alpha. APOBEC3G and APOBEC3F are cytidine deaminases that are able to strongly inhibit retroviral replication by at least two mechanisms. They are counteracted by the lentiviral Vif protein. TRIM5alpha binds to sensitive, incoming retroviruses via its C-terminal PRY/SPRY domain and rapidly recruits them to the proteasome before significant viral DNA synthesis can occur. Both of these proteins robustly block retroviral replication in a species-specific way. It remains an open but important question as to whether innate restriction factors such as these can be harnessed to inhibit HIV-1 replication in humans.
Huthoff
Hendrik
H
Department of Infectious Diseases, Guy's, King's and St Thomas' School of Medicine, London SE1 9RT, UK.
Towers
Greg J
GJ
D000071480:APOBEC-3G Deaminase; D000818:Animals; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins / Q000378:metabolism / Q000494:pharmacology*; D003564:Cytidine Deaminase / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D043525:Cytosine Deaminase / Q000378:metabolism / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008958:Models, Molecular; D012190:Retroviridae / Q000187:drug effects* / Q000502:physiology; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D014779:Virus Replication / Q000187:drug effects*
D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases; C492906:APOBEC3F protein, human; D043525:Cytosine Deaminase; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase