MYXOMA VIRUS AND MALIGNANT RABBIT FIBROMA VIRUS ENCODE A SERPIN-LIKE PROTEIN IMPORTANT FOR VIRUS VIRULENCE

被引：99

作者：

UPTON, C ^{[1
]}

MACEN, JL ^{[1
]}

WISHART, DS ^{[1
]}

MCFADDEN, G ^{[1
]}

机构：

[1] UNIV ALBERTA,DEPT BIOCHEM,EDMONTON T6G 2H7,ALBERTA,CANADA

来源：

VIROLOGY | 1990年 / 179卷 / 02期

关键词：

D O I：

10.1016/0042-6822(90)90129-F

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

The leporipoxviruses Shope fibroma virus (SFV), the myxoma virus (MYX), and the SFV/MYX recombinant malignant rabbit fibroma virus (MRV) are closely related yet induce profoundly different diseases in the European rabbit. SFV, which produces a benign tumor at the site of inoculation, is cleared by the immune system after approximately 2 weeks whereas MYX and MRV induce a rapidly lethal systemic infection characterized by generalized suppression of host immune functions. DNA sequencing studies reveal that MRV and MYX possess homologous gene members of the T6/T8/T9 family originally described in the terminal inverted repeat (TIR) of SFV. We also describe a gene present in both MYX and MRV genomes, but which has apparently evolved in the SFV genome into a fragmented pseudogene that appears to contribute to the aggressive nature of MYX and MRV infections. Translation of this open reading frame, designated MYXOMA SERPIN 1 (SERP1), reveals a protein sequence with highly significant homology to the super-family of serine protease inhibitors (serpins) which also includes a number of other poxviral proteins. In the MYX genome the SERP1 gene lies entirely within the TIR sequences and is thus present as two copies, while in the MRV genome SERP1 is present in the unique sequences adjacent to the TIR boundary and hence is a single copy. The amino acid homology between the putative active site of SERP1 and those of other serpins predicts that the target enzyme will be different from the known catalog of serine antiprotease substrates. Deletion of this gene from MRV significantly attenuates the disease spectrum induced by the normally lethal virus. Although the MRV-S1 deletion construct (MRV with SERP1 gene deleted) grows in all tissue culture cells tested in a fashion identical to the MRV parent, the majority of rabbits infected with MRV-S1 are able to mount an effective immune response and totally recover from the virus infection to become resistant to subsequent challenge by MRV or MYX. © 1990.

引用

页码：618 / 631

页数：14

共 49 条

[41] Tomley, Binns, Campbell, Boursnell, Sequence analysis of an 112 kilobase near-terminal BamHI fragment of fowlpox virus, Journal of General Virology, 69, pp. 1025-1040, (1988)
[42] Upton, Carrell, McFadden, A novel member of the serpin superfamily is encoded on a circular plasmid-like DNA species isolated from rabbit cells, FEBS Lett., 207, pp. 115-120, (1986)
[43] Upton, Macen, McFadden, Mapping and sequencing of a gene from myxoma virus that is related to those encoding epidermal growth factor and transforming growth factor alpha, J. Virol., 61, pp. 1271-1275, (1987)
[44] Upton, Macen, Maranchuk, Delange, McFadden, Tumorigenic poxviruses: Fine analysis of the recombination junctions in malignant rabbit fibroma virus, a recombinant between Shope fibroma virus and myxoma virus, Virology, 166, pp. 229-239, (1988)
[45] Upton, McFadden, DNA sequence homology between the terminal inverted repeats of Shope fibroma virus and an endogenous cellular plasmid species, Mol. Cell. Biol., 6, pp. 265-276, (1986)
[46] Upton, McFadden, Tumorigenic poxviruses: Analysis of viral DNA sequences implicated in the tumorigenicity of Shope fibroma virus and malignant rabbit virus, Virology, 152, pp. 308-321, (1986)
[47] Upton, McFadden, Identification and nucleotide sequence of the thymidine kinase gene of Shope fibroma virus, J. Virol., 60, pp. 920-927, (1986)
[48] Upton, Opgenorth, Traktman, McFadden, Identification and DNA sequence of the Shope fibroma virus DNA topoisomerase gene, Virology, 176, pp. 439-447, (1990)
[49] Yuen, Moss, Oligonucleotide sequence signaling transcriptional termination of vaccinia virus early genes, Proc. Natl. Acad. Sci. USA, 84, pp. 6417-6421, (1987)

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