MPXV intrahost variation in the context of APOBEC deamination: An initial look - Virological

[Mary Wilson]

June 13 2022

Anton Nekrutenko | galaxyproject.org 1, Penn State, CEFE CNRS

APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) converts C in single stranded stretches of DNA or RNA to U resulting C → T transition. Members of APOBEC family target specific sequence motifs: TC , CCC , TTC where the last base mutated to T , or TCW ( W = A / T ) where the middle base mutates to T (see Chen and MacCarthy 2014 1).

Recently O’Toole & Rambaut 3 conducted a survey of potential APOBEC signatures in a set of MPXV genomes. If APOBEC is indeed partially responsible for introducing nucleotide changes to MPXV genome in humans, we should be able to observe these changes in intrahost samples with intermediate alternative allele frequencies. ...

https://virological.org/t/mpxv-intr...apobec-deamination-an-initial-look/856#post_1

 

[Emily]

Dr. Malone pointed out this study that indicates that pox viruses wouldn't be susceptible to APOBEC enzymes. I looked for any work done that indicates otherwise, but found none.

https://virologyj.biomedcentral.com/articles/10.1186/1743-422X-3-86
Kremer, M., Suezer, Y., Martinez-Fernandez, Y. et al. Vaccinia virus replication is not affected by APOBEC3 family members. Virol J 3, 86 (2006). https://doi.org/10.1186/1743-422X-3-86

Abstract

Background

The APOBEC3G protein represents a novel innate defense mechanism against retroviral infection. It facilitates the deamination of the cytosine residues in the single stranded cDNA intermediate during early steps of retroviral infection. Most poxvirus genomes are relatively A/T-rich, which may indicate APOBEC3G-induced mutational pressure. In addition, poxviruses replicate exclusively in the cytoplasm where APOBEC3G is located. It was therefore tempting to analyze whether vaccinia virus replication is affected by APOBEC3G.
Results

The replication of vaccinia virus, a prototype poxvirus, was not, however, inhibited in APOBEC3G-expressing cells, nor did other members of the APOBEC3 family alter vaccinia virus replication. HIV counteracts APOBEC3G by inducing its degradation. However, Western blot analysis showed that the levels of APOBEC3G protein were not affected by vaccinia virus infection.
Conclusion

The data indicate that APOBEC3G is not a restriction factor for vaccinia virus replication nor is vaccinia virus able to degrade APOBEC3G.