Ectromelia virus is the causative agent of the disease mousepox. Mousepox is arguably the
best small animal model available for the study of smallpox. This model is under utilized
due to ectromelia virus' potential to cause explosive epizootics in mouse colonies;
however, with modern animal husbandry techniques and biocontainment facilities, these
concerns are no longer founded. The mousepox model is used to study basic questions in
pathogenesis, to evaluate prophylactic and therapeutic treatments for smallpox, and to
develop countermeasures to orthopoxviruses bioengineered for enhanced virulence,
transmissibility, or the ability to break-through vaccine immunity. Some of the “dual use”
knowledge gained from these experiments can be used for the improvement of human welfare
or, in the wrong hands, the generation of biological weapons. The Institutional Biosafety
Committee will likely become an important component in the evaluation of dual use
technology.
References
1.
BlandenR.
V. (1974). T cell
response to viral and bacterial infection. Transplantation
Reviews, 19,
56–88.
2.
BlandenR. V.GardnerI. D.
(1976). The cell-mediated immune response to ectromelia
virus infection. I. Kinetics and characteristics of the primary effector T cell response
in vivo. Cellular Immunology, 22,
271–282.
3.
BrayM.MartinezM.SmeeD. F.KefauverD.ThompsonE.HugginsJ. W.
(2000). Cidofovir protects mice against lethal aerosol or
intranasal cowpox virus challenge. Journal of Infectious
Diseases, 181,
10–19.
4.
BrownsteinD.
G. (1998). Comparative
genetics of resistance to viruses. American Journal of Human
Genetics, 62,
211–214.
5.
BrownsteinD. G.GrasL.
(1995). Chromosome mapping of Rmp-4, a gonad-dependent gene
encoding host resistance to mousepox. Journal of
Virology, 69,
6958–6964.
6.
BullerR. M.BhattP. N.WallaceG. D.
(1983). Evaluation of an enzyme-linked immunosorbent assay
for the detection of ectromelia (mousepox) antibody. Journal of
Clinical Microbiology, 18,
1220–1225.
7.
BullerR. M.PalumboG. J.
(1991). Poxvirus pathogenesis.
Microbiological Reviews, 55,
80–122.
8.
BullerR. M.PotterM.WallaceG. D.
(1986). Variable resistance to ectromelia (mousepox) virus
among genera of Mus. Current Topics in Microbiology &
Immunology, 127,
319–322.
9.
BullerR. M.WeinblattA. C.HamburgerA. W.WallaceG. D.
(1987). Observations on the replication of ectromelia virus
in mouse-derived cell lines: Implications for epidemiology of mousepox.
Laboratory Animal Science, 37,
28–32.
10.
ChenN.BullerR. M.WallE. M.UptonC.
(2000). Analysis of host response modifier ORFs of
ectromelia virus, the causative agent of mousepox. Virus
Research, 66,
155–173.
11.
ChenN.DanilaM. I.FengZ.BullerR. M.WangC.HanX.LefkowitzE. J.UptonC.
(2003). The genomic sequence of ectromelia virus, the
causative agent of mousepox. Virology,
317, 165–186.
12.
DelanoM. L.BrownsteinD.
G. (1995). Innate
resistance to lethal mousepox is genetically linked to the NK gene complex on chromosome
6 and correlates with early restriction of virus replication by cells with an NK
phenotype. Journal of Virology, 69,
5875–5877.
13.
DennisC.
(2001). The bugs of war.
Nature, 411,
232–235.
14.
DickE.
J.Jr.KittellC. L.MeyerH.FarrarP. L.RoppS. L.EspositoJ. J.BullerR. M.NeubauerH.KangY. H.McKeeA. E.
(1996). Mousepox outbreak in a laboratory mouse
colony. Laboratory Animal Science, 46,
602–611.
15.
EastI. J.GulyasB. J.DeanJ.
(1985). Monoclonal antibodies to the murine zona pellucida
protein with sperm receptor activity: Effects on fertilization and early
development. Developmental Biology,
109, 268–273.
16.
EpifanoO.LiangL. F.FamilariMMoosM. C.Jr.DeanJ.
(1995). Coordinate expression of the three zona pellucida
genes during mouse oogenesis. Development,
121, 1947–1956.
17.
FennerF.
(1948a). The clinical features and pathogenesis of mouse-pox
(infectious ectromelia of mice). The Journal of Pathology and
Bacteriology, 60,
529–551.
18.
FennerF.
(1948b). The pathogenesis of the acute exanthems. An
interpretation based on experimental investigations with mousepox (infectious ectromelia
of mice). The Lancet, ii,
915–920.
19.
FennerF.
(1982). Mousepox. In FosterH.
L.SmallJ. D.FoxJ. G.
(ed.). The mouse in biomedical research. New
York: Academic Press.
20.
FennerF.HendersonD. A.AritaI.JezekZ.LadnyjI. D.
(1988). Smallpox and its eradication.
Geneva: World Health
Organization.
21.
FennerF.WoodroofeG. M.
(1953). The pathogenesis of infectious myxomatosis: The
mechanism of infection and the immunological response in the European rabbit
(oryctolagus cuniculus). British Journal of Experimental
Pathology, 34,
400–411.
JacksonR. J.MaguireD. J.HindsL. A.RamshawI. A.
(1998). Infertility in mice induced by a recombinant
ectromelia virus expressing mouse zona pellucida glycoprotein 3.
Biological Reproduction, 58,
152–159.
24.
JacksonR. J.RamsayA. J.ChristensenC. D.BeatonS.HallD. F.RamshawI. A.
(2001). Expression of mouse interleukin-4 by a recombinant
ectromelia virus suppresses cytolytic lymphocyte responses and overcomes genetic
resistance to mouse-pox. Journal of Virology,
75, 1205–1210.
25.
JacobyR. O.BhattP. N.
(1987). Mousepox in inbred mice innately resistant or
susceptible to lethal infection with ectromelia virus. II. Pathogenesis.
Laboratory Animal Science, 37,
16–22.
26.
JacobyR. O.BhattP. N.BrownsteinD.
G. (1989). Evidence that
NK cells and interferon are required for genetic resistance to lethal infection with
ectromelia virus. Archives of Virology,
108, 49–58.
27.
KarupiahG.
(1998). Type 1 and type 2 cytokines in antiviral
defense. Veterinary Immunology & Immunopathology,
63, 105–109.
28.
KarupiahG.BullerR. M.Van RooijenN.DuarteC. J.ChenJ.
(1996). Different roles for CD4+ and CD8+ T lymphocytes and
macrophage subsets in the control of a generalized virus infection.
Journal of Virology, 70,
8301–8309.
29.
KarupiahG.FredricksonT. N.HolmesK. L.KhairallahL. H.BullerR. M.
(1993). Importance of interferons in recovery from
mousepox. Journal of Virology, 67,
4214–4226.
30.
LouY.AngJ.ThaiH.McElveenF.TungK. S.
(1995). A zona pellucida 3 peptide vaccine induces
antibodies and reversible infertility without ovarian pathology.
Journal of Immunology, 155,
2715–2720.
31.
MillarS. E.ChamowS. M.BaurA. W.OliverC.RobeyF.DeanJ.
(1989). Vaccination with a synthetic zona pellucida peptide
produces long-term contraception in female mice.
Science, 246,
935–938.
32.
MimsC. A.
(1964). Aspects of the pathogenesis of virus
diseases. Bacteriological Reviews, 28,
30–71.
33.
MossB.
(2001). Poxviridae: The viruses and their
replication. In KnipeD. M.HowleyP. M.
(eds.), Fields VirologyVolume 2, (pp. 2849–2883).
New York: Lippincott Williams and
Wilkins.
34.
MossmanK.UptonC.BullerR. M.McFaddenG.
(1995). Species specificity of ectromelia virus and vaccinia
virus interferon-gamma binding proteins. Virology,
208, 762–769.
35.
National Academy of Sciences. (In
Press). BioTechnology Research in an age of terrorism: Confronting the “dual use”
dilemma. Washington, DC:
National Academies Press.
36.
PayneL. G.KristenssonK.
(1985). Extracellular release of enveloped vaccinia virus
from mouse nasal epithelial cells in vivo. Journal of General
Virology, 66,
643–646.
37.
RobertsJ.
A. (1962a).
Histopathogenesis of mouse-pox. I. Respiratory infection.
British Journal of Experimental Pathology, 43,
451–461.
38.
RobertsJ.
A. (1962b).
Histopathogenesis of mouse-pox. II. Cutaneous infection.
British Journal of Experimental Pathology, 43,
462–468.
39.
RosengardA. M.LiuY.NieZ.JimenezR.
(2002). Variola virus immune evasion design: Expression of a
highly efficient inhibitor of human complement. Proceedings of
the National Academy of Sciences, USA, 99,
8808–8813.
40.
TuckerJ. B.ZilinskasR. A.
(in press). The 1971 smallpox epidemic in Aralsk, Kazakhstan, and the Soviet
biological warfare program. Monterey, CA:
Center for Nonproliferation Studies.
41.
Tyndale-BiscoeC.
H. (1994).
Virus-vectored immunocontraception of feral mammals.
Reproduction, Fertility and Development, 6,
281–287.
42.
WallaceG. D.BullerR. M.
(1985). Kinetics of ectromelia virus (mousepox) transmission
and clinical response in C57BL/6j, BALB/cByj and AKR/J inbred mice.
Laboratory Animal Science, 35,
41–46.
43.
WallaceG. D.WernerR. M.GolwayP. L.HernandezP. L.AllingD. W.GeorgeD. A.
(1981). Epizootiology of an outbreak of mousepox at the
National Institutes of Health. Laboratory Animal
Science, 31,
1–15.
44.
WehrleP. F.PoschJ.RichterK. H.HendersonD. A.
(1970). An airborne outbreak of smallpox in a German
hospital and its significance with respect to other recent outbreaks in
Europe. Bulletin of the World Health Organization,
43, 669–679.
