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PMID:8676463

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Citation

Mossman, K, Lee, SF, Barry, M, Boshkov, L and McFadden, G (1996) Disruption of M-T5, a novel myxoma virus gene member of poxvirus host range superfamily, results in dramatic attenuation of myxomatosis in infected European rabbits. J. Virol. 70:4394-410

Abstract

Myxoma virus is a pathogenic poxvirus that induces a lethal myxomatosis disease profile in European rabbits, which is characterized by fulminating lesions at the primary site of inoculation, rapid dissemination to secondary internal organs and peripheral external sites, and supervening gram-negative bacterial infection. Here we describe the role of a novel myxoma virus protein encoded by the M-T5 open reading frame during pathogenesis. The myxoma virus M-T5 protein possesses no significant sequence homology to nonviral proteins but is a member of a larger poxviral superfamily designated host range proteins. An M-T5- mutant virus was constructed by disruption of both copies of the M-T5 gene followed by insertion of the selectable marker p7.5Ecogpt. Although the M-T5- deletion mutant replicated with wild-type kinetics in rabbit fibroblasts, infection of a rabbit CD4+ T-cell line (RL5) with the myxoma virus M-T5- mutant virus resulted in the rapid and complete cessation of both host and viral protein synthesis, accompanied by the manifestation of all the classical features of programmed cell death. Infection of primary rabbit peripheral mononuclear cells with the myxoma virus M-T5-mutant virus resulted in the apoptotic death of nonadherent lymphocytes but not adherent monocytes. Within the European rabbit, disruption of the M-T5 open reading frame caused a dramatic attenuation of the rapidly lethal myxomatosis infection, and none of the infected rabbits displayed any of the characteristic features of myxomatosis. The two most significant histological observations in rabbits infected with the M-T5-mutant virus were (i) the lack of progression of the infection past the primary site of inoculation, coupled with the establishment of a rapid and effective inflammatory reaction, and (ii) the inability of the virus to initiate a cellular reaction within secondary immune organs. We conclude that M-T5 functions as a critical virulence factor by allowing productive infection of immune cells such as peripheral lymphocytes, thus facilitating virus dissemination to secondary tissue sites via the lymphatic channels.

Links

PubMed PMC190373

Keywords

Animals; Apoptosis; Base Sequence; CD4-Positive T-Lymphocytes/pathology; CD4-Positive T-Lymphocytes/virology; Cell Line; Cells, Cultured; Cloning, Molecular; DNA Primers; Defective Viruses/genetics; Female; Gene Deletion; Molecular Sequence Data; Myxoma virus/genetics; Myxoma virus/metabolism; Myxoma virus/pathogenicity; Myxomatosis, Infectious/pathology; Myxomatosis, Infectious/virology; Poxviridae/physiology; Rabbits; Sequence Homology, Amino Acid; Viral Proteins/genetics; Viral Proteins/physiology; Virulence/genetics; Virus Replication

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MYXVL:MT5

GO:0016032: viral process

ECO:0000315:

P

Figure 5. Defective growth of M-T5- virus in a CD4+ rabbit T-cell line (RL5).

complete
CACAO 8998

MYXVL:MT5

GO:0019050: suppression by virus of host apoptotic process

ECO:0000315:

P

Figure 7.

complete
CACAO 8999

MYXVL:MT5

involved_in

GO:0019050: suppression by virus of host apoptotic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

See also

References

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