Enhanced cytoplasmic sequestration of the nuclear export receptor CRM1 by NS2 mutations developed in the host regulates parvovirus fitness

Journal of Virology
Alberto López-BuenoJosé M Almendral

Abstract

To investigate whether a DNA virus can evade passive immunotherapy with a polyclonal antiserum, we analyzed the protection of a neutralizing capsid antiserum against a lethal infection of the immunosuppressive strain of the parvovirus minute virus of mice (MVMi) in 42 immunodeficient mice over a period of 200 days. A few mice were effectively protected, but most developed a delayed lethal leukopenic syndrome during the treatment or weeks afterwards. Unexpectedly, viruses isolated from treated but also from control leukopenic mice showed no amino acid changes throughout the entire capsid coding region, although the viral populations were genetically heterogeneous, mainly in the second exon of the coding sequence of the NS2 nonstructural protein. The NS2 point amino acid changes (T88A, K96E, L103P, and L153 M) that were consistently selected in several mice clustered within the nuclear exportin CRM1 binding domain, in a reading frame that did not alter the overlapping NS1 coding region. These mutations endowed emerging viruses with an increased fitness that was demonstrable by their relative resistance to the neutralizing capsid antiserum in a postentry plaque-forming assay, the rapid overgrowth of a competing wild-type (wt) popu...Continue Reading

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Citations

Apr 4, 2008·Molecular Biology of the Cell·Dieuwke EngelsmaMaarten Fornerod
Sep 5, 2008·Journal of Virology·Karin HoelzerColin R Parrish
Sep 4, 2007·Advances in Virus Research·Susan F Cotmore, Peter Tattersall
Oct 5, 2017·Viruses·Elina MäntyläMaija Vihinen-Ranta
Aug 11, 2021·Viruses·Salla MattolaMaija Vihinen-Ranta

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