Cell Cycle-independent Role of Cyclin D3 in Host Restriction of Influenza Virus Infection

• DOI: 10.1074/jbc.m117.776112
• Publication Date: 2017-01-28T02:25:20Z
• Authors: Ying Fan; Chris Ka-Pun Mok; Michael Chi Wai Chan; Yang Zhang; Béatrice Nal; François Kien; Roberto Bruzzone; Sumana Sanyal
• Keywords: Cyclin D3

To identify new host factors that modulate the replication of influenza A virus, we performed a yeast two-hybrid screen using cytoplasmic tail matrix protein 2 from highly pathogenic H5N1 strain. The revealed high-score interaction with cyclin D3, key regulator cell cycle early G1 phase. M2-cyclin D3 was validated through GST pull-down and recapitulated in A/WSN/33-infected cells. Knockdown Ccnd3 by small interfering RNA significantly enhanced virus progeny titers culture supernatants. Interestingly, increase production due to deficiency per se not merely consequence deregulation. combined knockdown Rb1, which rescued progression into S phase, failed normalize production. Infection triggered redistribution nucleus cytoplasm, followed its proteasomal degradation. When overexpressed HEK 293T cells, impaired binding M2 M1, is essential for proper assembly virions, lending further support role as putative restriction factor. Our study describes identification characterization novel interactor protein. We hypothesize competitive inhibition M1-M2 impairs infectious virion formation results attenuated In addition, provide mechanistic insights dynamic interplay machinery during infection.