Incorporation of mouse APOBEC3 into murine leukemia virus virions decreases the activity and fidelity of reverse transcriptase.
APOBEC3 proteins are restriction factors that induce G→A hypermutation in retroviruses during replication as a result of cytidine deamination of minus-strand DNA transcripts. However, the mechanism of APOBEC inhibition of murine leukemia viruses (MuLVs) does not appear to be G→A hypermutation and is unclear. In this report, the incorporation of mA3 in virions resulted in a loss in virion reverse transcriptase (RT) activity and RT fidelity that correlated with the loss of virion-specific infectivity.
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana, USA Department of Biomedical Sciences, University of Cagliari, Monserrato (Cagliari), Italy.
Stefano
S
Boi
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana, USA.
Angelo
A
Kolokithas
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana, USA.
Joyce
J
Shepard
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana, USA.
Rebecca
R
Linwood
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana, USA.
Kyle
K
Rosenke
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana, USA.
Erik
E
Van Dis
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana, USA.
Frank
F
Malik
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana, USA levans@niaid.nih.gov.
Leonard H
LH
Evans
D000818:Animals; D015153:Blotting, Western; D003564:Cytidine Deaminase / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008979:Moloney murine leukemia virus / Q000201:enzymology* / Q000472:pathogenicity; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism*; D012192:Retroviridae Infections / Q000201:enzymology* / Q000821:virology; D014162:Transfection; D014412:Tumor Virus Infections / Q000201:enzymology* / Q000821:virology; D014771:Virion / Q000472:pathogenicity*; D019065:Virus Assembly; D014779:Virus Replication
D012194:RNA-Directed DNA Polymerase; C503504:Apobec3 protein, mouse; D003564:Cytidine Deaminase