Biosynthesis of the IFN-gamma binding protein of ectromelia virus, the causative agent of mousepox.

Ectromelia virus (ECTV), the causative agent of mousepox, expresses an extracellular interferon-gamma binding protein (IFN-gammaBP) with homology to the ligand binding domains of the IFN-gamma high affinity receptor (IFN-gammaR1). Unlike the cellular receptor, the IFN-gammaBP binds IFN-gamma from several species. The IFN-gammaBP is synthesized early after infection, accumulating in the extracellular milieu as dimers composed of two protein species with Mr of 34.6 or 33.0 kDa. Homodimers are covalently linked by an interchain disulphide bond at position 216. The IFN-gammaBP has complex N-linked oligosaccharides at positions 41 and 149 as determined by site-directed mutagenesis and glycosidase treatment. Glycosylation at position 41 is required for secretion from mammalian cells and may play a role in the activity of the IFN-gammaBP. Glycosylation at position 149 is not required for secretion, and the lack of glycosylation at this site does not diminish ligand binding as measured by surface plasmon resonance (SPR) and ELISA.

Differential pathogenesis of lethal mousepox in congenic DBA/2 mice implicates natural killer cell receptor NKR-P1 in necrotizing hepatitis and the fifth component of complement in recruitment of circulating leukocytes to spleen.

Innate resistance of C57BL/6 (B6) mice to lethal mousepox is controlled by multiple genes. Previously, four resistance genes were localized to specific subchromosomal regions and transferred onto a susceptible DBA/2 (D2) background by serial backcrossing and intercrossing to produce congenic strains. Intraperitoneally inoculated ectromelia virus was uniformly lethal and achieved similar titers in B6 and D2 mice but elicited differential responses in liver, spleen, and circulating blood leukocytes. The distribution of these response phenotypes in congenic strains linked control of phenotypes with specific subchromosomal regions. D2.R1 mice, which carried a differential segment of chromosome 6, exhibited a B6 liver response and intermediate spleen and circulating leukocyte responses. D2.R2 and D2.R4 mice, which carried differential segments of chromosomes 2 and 1, respectively, exhibited a D2 liver response, a B6 spleen response, and an intermediate circulating leukocyte response. The localization of control of liver response phenotypes to chromosome 6 implicates cells that express natural killer (NK) cell receptor NKR-P1 alloantigens. The localization of control of spleen and circulating leukocyte responses to chromosomes 1, 2, and 6 implicates NK cells, the fifth component of complement, and a gene near the selectin gene complex in recruitment of circulating leukocytes to spleen.

Wallace P. Rowe lecture. Poxviruses of laboratory animals.

Currently the subfamily Chordopoxvirinae, the poxviruses of vertebrates, is subdivided into eight genera, containing some 20-30 species; an inexact figure because the birdpox viruses have not yet been properly investigated taxonomically. I have discussed seven species belonging to three genera, all of which have caused infection and usually disease in mammals commonly used in the laboratory. The list could have been extended had I included chickens and swine as laboratory animals, for that would have meant that I would have spoken about the birdpox viruses and swinepox virus as well. However, I think I have said enough to remind you of the importance of this family of viruses to those of you concerned with laboratory animal medicine. I believe that Wally Rowe would have been interested, for every case I have described presents problems in the ecology of viruses, and like my mentor Macfarlane Burnet, Wally approached virology from an ecological point of view, whether he was thinking about the DNA provirus of retroviruses and the host chromosome, the pathogenesis of disease, or the spread of viruses in animal populations, all topics to which he made major contributions.

Mousepox in inbred mice innately resistant or susceptible to lethal infection with ectromelia virus. II. Pathogenesis.

The pathogenesis of mousepox due to infection with ectromelia virus strain NIH-79 was characterized in genetically susceptible (BALB/cAnNCr) and genetically resistant (C57BL/6NCr) mice. BALB/c mice inoculated subcutaneous (s.c.) or intranasally (i.n.) had high mortality. Most mice died within 7 days from severe necrosis of the spleen and liver. Necrotic foci in livers of BALB/c mice that survived beyond 7 days often were accompanied by mononuclear cell infiltrates and by hyperplasia of lymphoid tissues. C57BL/6 mice inoculated by either route remained asymptomatic and necrotic lesions were mild or absent, whereas focal non-suppurative hepatitis and lymphoid hyperplasia were prominent. Infectious virus and viral antigen were distributed widely in tissues of BALB/c mice, but had limited distribution in C57BL/6 mice. Both mouse strains had infection of the respiratory tract, genital tract, oral tissues and bone marrow, and BALB/c mice also had infection of the intestines. Both strains also developed serum antibody to vaccinia virus antigen after infection. The results show that ectromelia virus occurs in tissues conducive to mouse to mouse transmission and that the severity and character of mousepox lesions correlate directly with resistance and susceptibility to infection. They also support the concept that cellular immunity contributes to survival from infection.