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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Pathogenic risk of endogenous retrovirus infection in immunodeficient hosts
Fengmin Zhang1, Rong Da, Wuqi Song
1Department of Microbiology and Parasitology, Harbin Medical University, Heilongjiang Province, Harbin 150086, China. fengminzhang@yahoo.com.cn
Abstract:
To investigate the pathogenic risk of endogenous retroviruses (ERVs) infection in immunodeficient hosts, the ERV of N-type ecotropic murine leukemia virus (MuLV) isolated from SL mice, a kind of mice containing considerable infectious ERV particles determined with SC-XC test and developing leukemia spontaneously with average of high frequency of 30% and incubation period of 315days, was inoculated intraperitoneally into newborn CBA nude mice. The distinct marker of splenomegaly for leukemia was observed in 33% of homozygous (nu/nu) and 17% of heterozygous (nu/+) of CBA nude mice with average incubation period of 310days and 432days post-inoculation, respectively. Furthermore, the ERV induced leukemia in both the SL mice and CBA nude mice was identified to be B lymphatic, transplantable and with rearrangement of the Evi-1 locus. The higher induction of leukemia and rearrangement of the Evi-1 locus in CBA nude mice are considered to be dependent on the lower immune status of the hosts. These findings indicate that the ERV could present the host immune dependent leukemogenesis in immunodeficient hosts through the Evi-1 gene rearrangement and suggest that screening of ERVs may be necessary in clinical transplantation or transfusion.
Insights
Endogenous retroviruses (ERVs) can cause leukemia in immunodeficient mice by rearranging the Evi-1 gene. Screening for ERVs is suggested for clinical transplantation and transfusion to prevent host immune-dependent leukemogenesis.
Area of Science:
- Virology
- Immunology
- Oncology
Background:
- Endogenous retroviruses (ERVs) are integrated into host genomes and can be transmitted vertically.
- Certain ERVs, like the N-type ecotropic murine leukemia virus (MuLV) from SL mice, are associated with spontaneous leukemia development.
- Immunodeficient hosts may be more susceptible to ERV-induced pathogenesis.
Purpose of the Study:
- To investigate the pathogenic risk of endogenous retroviruses (ERVs) infection in immunodeficient hosts.
- To determine if ERV infection can induce leukemia in CBA nude mice.
- To elucidate the mechanism of ERV-induced leukemogenesis.
Main Methods:
- Isolation of N-type ecotropic MuLV from SL mice.
- Intraperitoneal inoculation of MuLV into newborn CBA nude mice (homozygous and heterozygous).
- Monitoring for leukemia development (splenomegaly) and characterization of induced leukemia (B lymphatic, transplantable, Evi-1 locus rearrangement).
Main Results:
- Leukemia was observed in 33% of homozygous and 17% of heterozygous CBA nude mice post-inoculation.
- The induced leukemia was identified as B lymphatic, transplantable, and associated with Evi-1 locus rearrangement.
- Higher leukemia induction and Evi-1 locus rearrangement in CBA nude mice suggest dependence on host immune status.
Conclusions:
- Endogenous retroviruses can induce host immune-dependent leukemogenesis in immunodeficient hosts.
- Evi-1 gene rearrangement is a key mechanism in ERV-induced leukemia.
- Screening for ERVs may be necessary in clinical transplantation or transfusion settings to mitigate risks.
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