virology blog
About viruses and viral disease
TWiV travels to Rutgers University to speak with Brad, Kay, Siobain, and Kim about their careers and their work on viruses of plants, fungi, bacteria, diatoms, and coccolithophores.
Click arrow to play
Download TWiV 562 (77 MB .mp3, 127 min)
Subscribe (free): iTunes, Google Podcasts, RSS, email
Become a patron of TWiV!
Show notes at microbe.tv/twiv
By Gertrud U. Rey
Post-transcriptional gene silencing (PTGS) is an RNA regulation pathway in eukaryotes that depends on the presence of double stranded RNA (dsRNA) in the cytoplasm of cells. As stated by Nels Elde in TWiEVO 8, dsRNA in the cytoplasm has an effect synonymous to “blood in the water” for the innate immune system, triggering a cascade of events that leads to the degradation of complementary mRNAs. In plants, this pathway has been thought to serve as the predominant mechanism of antiviral defense.
Anne Simon joins the TWiV team to talk about plant viruses, including plum pox virus that devastates nut and stone fruit trees, and a geminivirus protein that regulates viral DNA synthesis.
Click arrow to play
Download TWiV 512 (62 MB .mp3, 103 min)
Subscribe (free): iTunes, Google Podcasts, RSS, email
Become a patron of TWiV!
Show notes at microbe.tv/twiv
Chemical modification of RNA by the addition of methyl groups is known to alter gene expression without changing the nucleotide sequence. The addition of a methyl group to adenosine has been found to regulate gene expression of animal viruses, and most recently of plant viruses.
The illustration shows a methyl (CH3-) group added to the nitrogen  that is attached to the #6 carbon of the purine base adenine. The entire molecule, with the ribose, is called N6-methyladenosine (m6A). Methylation of adenosine is carried out by enzymes that bind the RNA in the cell cytoplasm.
The m6A modification is found in multiple RNAs of most eukaryotes. It has also been found in the genome of RNA animal viruses. The modification is added to RNAs by a multi-protein enzyme complex, and is removed by demethylases. Silencing of the methylases decreases HIV-1 replication, while depletion of demethylases has the opposite effect. The replication of other viruses, including hepatitis C virus and Zika virus, is also regulated by m6A modification, but the details differ. For example, m6A negatively affects the replication of the flaviviruses hepatitis C virus and Zika virus.
Methylation of adenosine has been recently shown to modulate the replication of plant viruses. The RNA genomes of alfalfa mosaic virus (AMV) and cucumber mosaic virus (CMV) were found to contain m6A. An m6A demethylase was identified in Arabidopsis thaliana, a small flowering plant commonly used in research. This demethylase protein bound the capsid protein of AMV but not of CMV. Elimination of the demethylase from Arabidopsis reduced the replication of AMV but not CMV. These results show that m6A methylation negatively regulates the replication of AMV. Binding of the AMV capsid protein to the m6A demethylase might be a mechanism for ensuring that the enzyme demethylates viral RNA, allowing for efficient viral replication.
While it is clear that m6A regulates the replication of RNA viruses, the mechanisms involved are not well understood. Methylation of adenosine is likely to affect multiple functions, including the structure, celllular localization, splicing, stability, and translation of viral RNA (link to review). As m6A is also found in cellular RNAs, studies of its effect on viral processes is likely to provide insight into its role in cellular biology.
We recorded This Week in Virology #202 at the University of Nebraska in Lincoln, Nebraska on 5 October 2012, as part of the 12th Annual Symposium in Virology. Terence Dermody, Shou-Wei Ding, Grant McFadden and I spoke about our research, and then we recorded TWiV with University of Nebraska virologists James Van Etten, T. Jack Morris, and Charles Wood.
I was impressed by the fine virology being done at the Nebraska Center for Virology, as well as the collegiality of the virology community in Nebraska, Iowa, South Dakota, and Kansas – Symposium attendees were from all of those states! I met many young virologists at the poster session and I was touched by how many of them wanted to say hello and thank us for doing TWiV.
Many thanks to all the virologists who came to the Symposium and stayed to watch TWiV. Special thanks to Charles Wood, the Director of the Nebraska Center for Virology, who participated in TWiV #202 along with T. Jack Morris and James Van Etten.
Here are some behind the scenes photographs of this short but very informative visit.
