IFITM3 restricts the morbidity and mortality associated with influenza

Nature 484, 519–523 (26 April 2012)

Speaker: Nai-Huei Jhong (鍾乃惠)                                       Time:14:00~15:00,Oct.03, 2012

Commentator: Dr. Chung-Hsin Tseng (曾忠信老師)          Place: Room 601

Abstract

Interferon-induced transmembrane protein 3 (IFITM3) is the host cell modifier to defense against virus infection. It has been shown previously that IFITM3 can restrict the replication of influenza A virus, dengue virus, and West Nile virus in host cells¹. The IFITM protein can be inducible by type I and IIinterferons, two well-known cytokine with anti-viral activity. However, the role of IFITM protein in anti-viral defense in vivo is still unclear. In this study, the authors used knockout mice to study the effect of IFITM3 in the host protection. When the IFITM3 knockout mice were treated with low-pathogenic influenzavirus, these mice had serious pneumonia, hemorrhagic pleural effusion, and multiple lesions in all lung lobes. This result could mirror the destruction inflicted by the highly pathogenic 1918 ‘Spanish’ influenza. Analysis of lung tissue cell populations in the IFITM3^-/- animals on day 6 post-infection showed a significant reduction in the proportions of CD4⁺ cells, CD8⁺ T cells, and natural killer (NK) cells, as well as increased proportions of neutrophils compared with wild-type infected mice. Subsequently, they analyzed Ifitm3 alleles of hospitalized patients during 2009 influenza pandemic. They found the enrichment of the minor allele in those hospitalized with influenza infection. Cells with minor allele homozygous expressed low levels of IFITM3 and increased infection in vitro. Collectively, their results show that IFITM3 is a critical factor to protect hosts from influenza virus infection. In the future, with genetic screening available, patients who carry the variant of the gene may be treated with preventive vaccines.

References

1.    Abraham L. Brass., et al., The IFITM Proteins Mediate Cellular Resistance to Influenza A H1N1 Virus,West Nile Virus, and Dengue Virus. Cell. 2009 December 24; 139(7): 1243–1254