Differential roles for the C-terminal hexapeptide domains of NS2 splice variants during MVM infection of murine cells

Virology
Zandra RuizPeter Tattersall

Abstract

The MVM NS2 proteins are required for viral replication in cells of its normal murine host, but are dispensable in transformed human 324K cells. Alternate splicing at the minor intron controls synthesis of three forms of this protein, which differ in their C-terminal hexapeptides and in their relative abundance, with NS2P and NS2Y, the predominant isoforms, being expressed at a 5:1 ratio. Mutant genomes were constructed with premature termination codons in the C-terminal exons of either NS2P or NS2Y, which resulted in their failure to accumulate in vivo. To modulate their expression levels, we also introduced a mutation at the putative splice branch point of the large intron, dubbed NS2(lo), that reduced total NS2 expression in murine A9 cells such that NS2P accumulated to approximately half the level normally seen for NS2Y. All mutants replicated productively in human 324K cells. In A9 cells, NS2Y(-) mutants replicated like wildtype, and the NS2(lo) mutants expressed NS1 and replicated duplex viral DNA like wildtype, although their progeny single-strand DNA synthesis was reduced. However, while NS2P(-) and NS2-null viruses initiated infection efficiently in A9 cells, they gave diminished NS1 levels, and viral macromolecular sy...Continue Reading

References

Jan 8, 1999·The Journal of General Virology·T OhshimaK Yagami
Oct 21, 1999·Biochemical and Biophysical Research Communications·T OhshimaK i Yagami
Oct 17, 2001·Journal of Virology·A Op De BeeckP Caillet-Fauquet
May 22, 2002·Journal of Virology·Philip J YoungChristian L Lorson
Nov 15, 2002·The New England Journal of Medicine·William C Hahn, Robert A Weinberg
Jun 29, 2004·Journal of Virology·Brian D PooleStanley J Naides

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Citations

Nov 3, 2014·Annual Review of Virology·Susan F Cotmore, Peter Tattersall

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