4.4 Article

Mutation of the Myxoma virus SERP2 P1-site to prevent proteinase inhibition causes apoptosis in cultured RK-13 cells and attenuates disease in rabbits, but mutation to alter specificity causes apoptosis without reducing virulence

期刊

VIROLOGY
卷 356, 期 1-2, 页码 12-22

出版社

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2006.07.049

关键词

Myxoma virus; poxvirus; serpin; proteinase; protease; caspase; apoptosis; inflammation; pathogenesis; virulence

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资金

  1. NIAID NIH HHS [AI-15722] Funding Source: Medline
  2. NIDCR NIH HHS [DE-07200] Funding Source: Medline

向作者/读者索取更多资源

Myxoma virus (MYX) prevents apoptosis in RK-13 cells and forms thick dermal lesions with 100% mortality in rabbits. MYX encodes the virulence factor SERP2, a serine proteinase inhibitor (serpin). SERP2 was mutated to evaluate SERP2 function during MYX infection. MYX Delta SERP2::lacZ (deleted for SERP2) did not inhibit apoptosis in RK-13 cells; infected rabbits had thin dermal lesions and < 10% mortality. MYX-SERP2-D294A, a P1-site aspartate to alanine mutant, inactivated the serpin; infection was indistinguishable from MYX Delta SERP2::lacZ. SERP2-D294E prevented inhibition of caspase-8, caspase-10 and granzyme-B; and MYX-SERP2-D294E failed to block apoptosis in RK-13 cells, but was fully virulent in rabbits. MYX Delta SERP2::crmA expressed crmA instead of SERP2 and inhibited apoptosis in cell culture, but caused thin lesions and only 70% mortality in rabbits, hence crmA cannot fully substitute for SERP2. Control of apoptosis in culture does not correlate with virulence in rabbits. Virulence may instead depend on inhibition of proinflammatory proteinases by SERP2. (c) 2006 Elsevier Inc. All rights reserved.

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