Communicated by: Kasturika Shankar & Lars-Anders Carlsson, Umeå University
An upstream protein-coding region in enteroviruses modulates virus infection in gut epithelial cells
Findings from the Firth group at Cambridge University, UK, challenge the existing dogma of a single polyprotein gene expression of enteroviruses. Initiated by an upstream ORF in a second reading frame, a previously overlooked, due to small size and/or amount, putative transmembrane protein of around 75 amino acids was found to be expressed in the studied Echovirus 7 and Poliovirus 1. The sequence of this ORF was well conserved in enteric enteroviruses including PV1, but not in rhinoviruses or in respiratory enteroviruses. In EV7, the protein enhanced infection of human intestinal organoids. The authors suggest that this newly discovered enteroviral transmembrane protein is involved in virus particle release from intracellular vesicles during intestinal infection.
Lulla V, Dinan AM, Hosmillo M, Chaudhry Y, Sherry L, Irigoyen N, Nayak KM, Stonehouse NJ, Zilbauer M, Goodfellow I, Firth AE. An upstream protein-coding region in enteroviruses modulates virus infection in gut epithelial cells. Nat Microbiol. 2019 Feb;4(2):280-292. doi: 10.1038/s41564-018-0297-1. PMID: 30478287
A second open reading frame in human enterovirus determines viral replication in intestinal epithelial cells
This report from Wei and coauthors at the Jilin University in China replicates, broadens and deepens the findings reported above. By alanine scanning mutagenesis, they defined an essential functional domain (WIGHPV) in the N-terminal part of the same protein (ORF2p) expressed by EV-A71. Furthermore, they have pinpointed the functional role of ORF2p to the release of infectious virus particles from intestinal cell lines and from primary cultures of intestinal epithelial cells. Thus, the protein is a virulence factor that plays a critical role at the late egress stage of enteroviral replication in the gut.
Guo H, Li Y, Liu G, Jiang Y, Shen S, Bi R, Huang H, Cheng T, Wang C, Wei W. A second open reading frame in human enterovirus determines viral replication in intestinal epithelial cells. Nat Commun. 2019 Sep 6;10(1):4066. doi: 10.1038/s41467-019-12040-9. PMID: 31492846
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Measles Vaccine Virus RNA in Children More Than 100 Days after Vaccination. McMahon J, Mackay IM, Lambert SB. Viruses. 2019 Jul 10;11(7). pii: E636. doi: 10.3390/v11070636. PMID: 31295941