Host-Specific Restriction of Avian Influenza Virus Caused by Differential Dynamics of ANP32 Family Members

• Published in: The Journal of infectious diseases Vol. 221; no. 1; pp. 71 - 80
• Main Authors: Park, Young Hyun, Chungu, Kelly, Lee, Su Bin, Woo, Seung Je, Cho, Ho Yeon, Lee, Hong Jo, Rengaraj, Deivendran, Lee, Ji-Ho, Song, Chang-Seon, Lim, Jeong Mook, Han, Jae Yong
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.01.2020
• Subjects: Avian flu; CRISPR; Genome editing; Genomes; Influenza; influenza virus; host restriction; ANP32 family; cellular host factor
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiz506

Abstract Background Influenza viruses must utilize host factors to complete their lifecycle. Species-specific differences in host factors between birds and mammals mean that avian influenza viruses (AIVs) replicate well in avian hosts but not in human hosts. Acidic nuclear phosphoprotein 32 family member A (ANP32A) has been identified as the host restriction factor for the viral polymerase (vPol) activity of AIVs. The ANP32A belongs to the conserved ANP32 family, the functional roles of which during viral replication remain unclear. Methods In this study, we targeted chicken ANP32A using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated genome editing to examine the functional roles of ANP32A and other members of the ANP32 family. Results We showed that chicken ANP32A only, not ANP32B and ANP32E, plays a pivotal role in supporting vPol activity of AIVs. Furthermore, we found that the human ANP32C, ANP32D, and ANP32E have suppressive effects on vPol activity in contrast to human ANP32A and ANP32B. Conclusions Chicken and human ANP32 family members had different effects on vPol activity, suggesting that species-specific vPol activity of AIVs could be caused by the differential functions and overall competency of ANP32 family members. Genetic differences in ANP32A between chicken and humans and the differential effects of ANP32 family members on influenza virus replication could result in PB2-627 residue-dependent host restriction.