Molecular cloning and characterization of APOBEC3 family in tree shrew

Gene. 2018 Mar 10;646:143-152. doi: 10.1016/j.gene.2017.12.060. Epub 2017 Dec 30.

Abstract

The APOBEC3 family is a series antiviral factors that inhibit the replication of many viruses, such as HIV-1 and HBV. Tree shrews (Tupaia belangeri) possess great potential as an animal model for human diseases and therapeutic responses. However, the APOBEC3 family is unknown in tree shrews. Recent work has showed the presence of the APOBEC3 family in tree shrews. In this work, the cDNA sequences of five APOBEC3 members were identified in tree shrews, namely, tsAPOBEC3A, -3C, -3F, -3G and -3H. The results showed that their sequences encoded a zinc (Z)-coordinating-domain as a characteristic of APOBEC3 proteins. Phylogenetic analysis revealed that the tree shrew APOBEC3 (tsAPOBEC3) genes have occurred independently and that they are clustered with other mammalian APOBEC3 members. Transcript expression analysis indicated that tsAPOBEC3 genes are constitutively expressed, and high in immune-related tissues. tsAPOBEC3 gene expression was up-regulated in hepatocytes and PBMCs by IFN-α stimulation. Finally, tsAPOBEC3 proteins could edit both sides of DNA by inserting G→A and C→T hypermutations. Overall, the results suggest that the tsAPOBEC3 family could play a key role in defense immunity through distinct editing mechanisms. Our results provided insights into the genetic basis for the development of a tree shrew model for studying viral infection. Future studies will focus on deepening our understanding on the antiviral functions of these editing enzymes in tree shrew.

Keywords: APOBEC3; Cytidine deaminase; Innate immunity; Restriction factor; Tree shrew.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cloning, Molecular / methods*
  • Conserved Sequence
  • Cytidine Deaminase / chemistry
  • Cytidine Deaminase / genetics*
  • Cytidine Deaminase / metabolism*
  • Gene Expression Regulation, Enzymologic
  • Hep G2 Cells
  • Hepatocytes / metabolism
  • Humans
  • Immunity
  • Leukocytes, Mononuclear / metabolism
  • Multigene Family
  • Phylogeny
  • Protein Domains
  • Tissue Distribution
  • Tupaiidae / genetics
  • Tupaiidae / immunology
  • Tupaiidae / metabolism*

Substances

  • Cytidine Deaminase