Mousepox in inbred mice innately resistant or susceptible to lethal infection with ectromelia virus. IV. Studies with the Moscow strain

Bhatt, P. N.; Jacoby, Robert O.; Gras, L

doi:10.1007/bf01487685

Cited by 25 publications

(35 citation statements)

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“…The Moscow strain of ectromelia virus is more virulent than the NIH 79 strain based on comparisons of several parameters including IDs0-LDs0 differences and peak titers [2,3]. In the context of the present study, one possible reason for this greater virulence is that the Moscow strain can evade or overwhelm a genetically determined host resistance mechanism to which the NIH 79 strain is vulnerable.…”

Section: Discussionmentioning

confidence: 97%

“…In genetically susceptible outbred, randombred and inbred strains of mice, the pathogenesis of ectromelia virus infection mimics that of fulminant variola virus infection and served as the definitive model of smallpox infection [-5, 6]. In genetically resistant strains, infection is usually inapparent [2]. The mechanisms which underlie these differences in susceptibility to lethal ectromelia virus infection are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

“…Hybrid crosses produced at Yale were F1 x D2, D2 x FI, and (Fl x Ft)F2. AII mice were housed and cared for as described previously [3] and were free of spontaneous murine infections as determined by periodic serological surveillance.…”

Section: Introductionmentioning

confidence: 99%

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Mousepox in inbred mice innately resistant or susceptible to lethal infection with ectromelia virus V. Genetics of resistance to the Moscow strain

Brownstein

Bhatt

Jacoby

1989

Archives of Virology

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The genetics of resistance to the Moscow strain of ectromelia virus was examined in crosses derived from resistant C57BL/6 (B6) and susceptible DBA/2 (D2) mice. Infection with 10(1) to 10(5) PFU of virus resulted in mortalities of 90 to 100% of D2, 0% of B6 and 0 to 3% of (B6 x D2) F1 mice by day 21. Among F1 x D2 backcross progeny, 49% of male and 18% of female mice died. Reciprocal backcrossing did not alter male or female mortality rates. These data are consistent with a single autosomal dominant gene controlling resistance to ectromelia in male mice and at least one additional dominant sex-limited gene controlling resistance in female mice. Fewer male F2 mice died than were predicted based on single-locus control and 32% of recombinant inbred (RI) strains derived from B6 and D2 progenitors expressed non-parental phenotypes. Therefore, additional resistance genes, not expressed in backcross mice, were apparently expressed in F2 mice and RI strains.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Mousepox in inbred mice innately resistant or susceptible to lethal infection with ectromelia virus V. Genetics of resistance to the Moscow strain

Brownstein

Bhatt

Jacoby

1989

Archives of Virology

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“…Newborn and infant mice are highly susceptible to WT of ectromelia (mousepox) virus (ECTV) and the empirically selected VACV [1][2][3]. Resistance to ECTV varies between mouse strains; C57BL/6 are one of the genetically more resistant strains.…”

Section: Introductionmentioning

confidence: 99%

Long‐lasting immunity by early infection of maternal‐antibody‐protected infants

et al. 2009

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Newborn higher vertebrates are largely immuno-incompetent and generally survive infections -including poxviruses -by maternal antibody protection. Here, we show that mice survived epidemics as adults only if exposed to lethal orthopoxvirus infections during infancy under the umbrella of maternal protective antibodies. This implies that both the absence of exposure to infection during early infancy or of effective vaccination renders the population highly susceptible to new or old re-emerging pathogens.Key words: Ectromelia . Maternal antibody . Protection . Vaccination . Vaccinia IntroductionIn the last 50 years, several viral diseases have been largely confined or even eradicated, as in the case of smallpox (variola virus) for which routine vaccinations with vaccinia virus (VACV) have been subsequently stopped in the 1970s. Due to loss of regular exposure to immunizing viral antigens, herd immunity might wane and leave the population susceptible to pathogen reemergence. Therefore, the consequences of interruption of the natural re-exposure cycles in the absence of infectious antigen contact need to be better understood.For these studies, we used orthopoxvirus infections because in both humans and mice the species-specific pox virus has devastating consequences with mortalities reaching 50-80% in the 14th century in Europe or up to 100% for certain mouse colonies in research establishments. Newborn and infant mice are highly susceptible to WT of ectromelia (mousepox) virus (ECTV) and the empirically selected VACV [1][2][3]. Resistance to ECTV varies between mouse strains; C57BL/6 are one of the genetically more resistant strains. Orthopox viruses such as variola virus, VACV, and ECTV share the cross-reactive neutralizing protective epitope [4] in addition to many T-cell specificities. Accordingly, vaccination with VACV provides solid protection to smallpox or mousepox (named sometimes ''smallpox of mice'') [5,6]. In this paper, we describe that long-lasting immunological protection results after immuno-incompetent pups of immune mice encounter an otherwise lethal pox-virus infection. Results and discussionWe compared survival of Moscow strain of Ectromelia virus (ECTV-MOS) infection at the age of 12-42 wk when specific pathogen-free infant C57BL/6 (H-2 b ) mice from immune mothers had been exposed to a lethal orthopox virus infection within the first days of life or not. C57BL/6 dams were immunized with 2 Â 10 6 pfu of VACV WR (LD50$10 8 pfu). Four weeks later they were mated with normal male mice. The newborn pups were infected intranasally at day 1 of age with 3-10 LD 50 corresponding to about 10 3 pfu of VACV WR ( We do not define maternal antibodies as the sole effector mechanism in this study, although they are the only ones transferred from the mother to the offspring. The theoretical possibility that viral antigen persisting in the mother could have been transferred to immunize newborns is unlikely because first, mothers were vaccinated 4 wk before pregnancy and second, without challenge infection early a...

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“…Infection of the skin results in the characteristic rash and pock lesions that resemble those found after VARV infection of humans. Also reminiscent of smallpox is the observation that some mouse strains are resistant to lethal infection (e.g., C57BL/6), while other strains (e.g., BALB/c) are susceptible and succumb to mousepox at very high rates (4).…”

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confidence: 99%

Comparable Polyfunctionality of Ectromelia Virus- and Vaccinia Virus-Specific Murine T Cells despite Markedly DifferentIn VivoReplication and Pathogenicity

Hersperger

Siciliano

Eisenlohr

2012

J Virol

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Vaccinia virus (VACV) stimulates long-term immunity against highly pathogenic orthopoxvirus infection of humans (smallpox) and mice (mousepox [ectromelia virus {ECTV}]) despite the lack of a natural host-pathogen relationship with either of these species. Previous research revealed that VACV is able to induce polyfunctional CD8 ؉ T-cell responses after immunization of humans. However, the degree to which the functional profile of T cells induced by VACV is similar to that generated during natural poxvirus infection remains unknown. In this study, we monitored virus-specific T-cell responses following the dermal infection of C57BL/6 mice with ECTV or VACV. Using polychromatic flow cytometry, we measured levels of degranulation, cytokine expression (gamma interferon [IFN-␥], tumor necrosis factor alpha [TNF-␣], and interleukin-2 [IL-2]), and the cytolytic mediator granzyme B. We observed that the functional capacities of T cells induced by VACV and ECTV were of a similar quality in spite of the markedly different replication abilities and pathogenic outcomes of these viruses. In general, a significant fraction (>50%) of all T-cell responses were positive for at least three functions both during acute infection and into the memory phase. In vivo killing assays revealed that CD8 ؉ T cells specific for both viruses were equally cytolytic (ϳ80% target cell lysis after 4 h), consistent with the similar levels of granzyme B and degranulation detected among these cells. Collectively, these data provide a mechanism to explain the ability of VACV to induce protective T-cell responses against pathogenic poxviruses in their natural hosts and provide further support for the use of VACV as a vaccine platform able to induce polyfunctional T cells.

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Mousepox in inbred mice innately resistant or susceptible to lethal infection with ectromelia virus. IV. Studies with the Moscow strain

Cited by 25 publications

References 7 publications

Mousepox in inbred mice innately resistant or susceptible to lethal infection with ectromelia virus V. Genetics of resistance to the Moscow strain

Mousepox in inbred mice innately resistant or susceptible to lethal infection with ectromelia virus V. Genetics of resistance to the Moscow strain

Long‐lasting immunity by early infection of maternal‐antibody‐protected infants

Comparable Polyfunctionality of Ectromelia Virus- and Vaccinia Virus-Specific Murine T Cells despite Markedly DifferentIn VivoReplication and Pathogenicity

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