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Mx1 and Mx2 key antiviral proteins are surprisingly lost in toothed whales

Viral outbreaks in dolphins and otherDelphinoideafamily members warrant investigation into the integrity of the cetacean immune system. The dynamin-like GTPase genes Myxovirus 1 (Mx1) andMx2defend mammals against a broad range of viral infections. Loss of Mx1 function in human and mice enhances... Full description

1st Person: Braun, Benjamin A.
Additional Persons: Marcovitz, Amir; Camp, J. Gray; Jia, Robin; Bejerano, Gill
Source: in Proceedings of the National Academy of Sciences of the United States of America Vol. 112, No. 26 (2015), p. 8036-8040
More Articles
Type of Publication: Article
Language: English
Published: 2015
Keywords: gene loss
Mx genes
cetaceans
immune system
toothed whales
Online: Volltext
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520 |a Viral outbreaks in dolphins and otherDelphinoideafamily members warrant investigation into the integrity of the cetacean immune system. The dynamin-like GTPase genes Myxovirus 1 (Mx1) andMx2defend mammals against a broad range of viral infections. Loss of Mx1 function in human and mice enhances infectivity by multiple RNA and DNA viruses, including orthomyxoviruses (influenza A), paramyxoviruses (measles), and hepadnaviruses (hepatitis B), whereas loss of Mx2 function leads to decreased resistance to HIV-1 and other viruses. Here we show that bothMx1andMx2have been rendered nonfunctional inOdontoceticetaceans (toothed whales, including dolphins and orcas). We discovered multiple exon deletions, frameshift mutations, premature stop codons, and transcriptional evidence of decay in the coding sequence of bothMx1andMx2in four species ofOdontocetes. We trace the likely loss event for both proteins to soon after the divergence ofOdontocetesandMystocetes(baleen whales) ∼33–37 Mya. Our data raise intriguing questions as to what drove the loss of bothMx1andMx2genes in theOdontocetilineage, a double loss seen in none of 56 other mammalian genomes, and suggests a hitherto unappreciated fundamental genetic difference in the way these magnificent mammals respond to viral infections. 
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