6/7 hours (another 2/3 hrs in writing this entry) ... searching through net.... lots of research papers... At last, I've figured it out.Yesterday, SRK was taking her lecture on plus strand RNA virus: Poliovirus and its life cycle.
The genome length of this novel (!!!) virus is 7500 b (According to SRK, but I think it varies. I've seen the range 7440 to 7700 b in different research papers.) Some features of Poliovirus genome are given below:
1. It has a covalently attached protein, VPg, at its 5' end. (1
2. Poly (A) tail at 3' end.
3. Three types of genes are present in this monocistronic genome: Structural, Protease (or proteinase) and RNA polymerase (from 5' to 3' respectively.) These genes are translated as single long polyprotein (~247 kD).
(right click and open in new window or tab to view enlarged image)
4. The proteinase has autosplicing capability. At first, it splices out itself, then it cleaves the polypeptide into different structural proteins and enzymes.
The list can be made much longer.
SRK said, poly (A) tail is required for infectivity, but VPg isn't. Later she said, RNA strand without covalently attached VPg can't be incorporated into viral capsid in maturation stage. I thought there was something missing... but I preferred not to ask. But this time Shammu was the person. She asked,"How can a RNA virus (or its RNA) be infective when it can't be inserted into viral capsid?" It was a good question, and I think I gave the answer in the class. But SRK didn't get my answer. Actually she didn't get the question either. She checked her lecture sheet and a book she brought with her (most probably Brock's Microbiology), then she dismissed one of her previous words. She thought it was her old book which is responsible. She told, "Forget about the sentence, "RNA with VPg can't be transcribed."...Well, Well, Well... this is another new statement. I don't think she told this before! May be I've missed.
So how to solve the puzzle. Remember none of her statements were wrong.
I've read some research papers published in different journals in between 1977 and 2006. The riddle is nearly solved ;)
VPg acts as a primer for new RNA strand synthesis (for both"+" and "-" strand synthesis.(2,3
So what about translation? Before translation, VPg is cleaved by cellular enzymes. RNAs attached to VPg can't be translated. The reason isn't still known, but it is thought that VPg interferes with some steps in translation. (2
Update: cre isn't necessary for translation, rather it is required for replication. cre is located within IRES but mutation in conserved cre region (AAACA motif) doesn't effect the rate of translation. (4
Hurray! The dilemma is solved at last. Polio RNA without VPg is infectious since it can carry out penetration, translation, synthesize new VPg protein which can act as primer for new RNA synthesis by RDR. So infection continues... but this RNA can't be incorporated in Capsid in maturation phase! Who cares that? It is creating effective progeny, it is infecting its host, effectively stopping host translation... Fantastic Job! But the poor RNA itself dies with its host. An altruist.
Image Courtesy:
Poliovirus:
http://users.wfu.edu/banklm3/cell/index.html
Translation in Poliovirus:
http://pathmicro.med.sc.edu/book/virol-sta.htm
References:
1. Yuan Fon Lee et al., A Protein Covalently Linked to Poliovirus Genome RNA, 1977;74;59-63 PNAS oi:10.1073/pnas.74.1.59.
2. Akio Nomoto et al., The 5'-terminal Structures of Poliovirion RNA and Poliovirus mRNA Differ Only in the Genome-Linked Protein VPg, Proc. Natl. Acad. Sci. USA, Vol. 74, No. 12, pp. 5345-5349, December 1977.
3. Timothy J.R. Harris et al. Nucleic Acids Research, Vol. 8, No. 6, 1980.
4. Mason et al., Identificationand Characterizationofa cis-Acting Replication Element (cre) Adjacent to the Internal Ribosome Entry Site of Foot-and-Mouth Disease Virus, JOURNAL OF VIROLOGY, Oct. 2002, p. 9686–9694
2 comments:
Bravo :)
nice!!
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