Endogenous MMTV Proviruses Induce Susceptibility to Both Viral and Bacterial Pathogens

PLoS Pathogens

Sanchita Bhadra¹  Shelley M Payne¹  Jaquelin P Dudley¹  Mary M Lozano¹ 

[1] Section of Molecular Genetics and Microbiology and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas, United States of America

关键词: T cells;    Vibrio cholerae;    Immune response;    Enzyme-linked immunoassays;    Antibodies;    Mammalian genomics;    Polymerase chain reaction;    Reverse transcriptase-polymerase chain reaction;   

DOI  :  10.1371/journal.ppat.0020128

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Most inbred mice carry germline proviruses of the retrovirus, mouse mammary tumor virus (MMTV) (called Mtvs), which have multiple replication defects. A BALB/c congenic mouse strain lacking all endogenous Mtvs (Mtv-null) was resistant to MMTV oral and intraperitoneal infection and tumorigenesis compared to wild-type BALB/c mice. Infection of Mtv-null mice with an MMTV-related retrovirus, type B leukemogenic virus, also resulted in severely reduced viral loads and failure to induce T-cell lymphomas, indicating that resistance is not dependent on expression of a superantigen (Sag) encoded by exogenous MMTV. Resistance to MMTV in Mtv-null animals was not due to neutralizing antibodies. Further, Mtv-null mice were resistant to rapid mortality induced by intragastric inoculation of the Gram-negative bacterium, Vibrio cholerae, but susceptibility to Salmonella typhimurium was not significantly different from BALB/c mice. Susceptibility to both MMTV and V. cholerae was reconstituted by the presence of any one of three endogenous Mtvs located on different chromosomes and was associated with increased pathogen load. One of these endogenous proviruses is known to encode only Sag. Therefore, Mtv-encoded Sag appears to provide a unique genetic susceptibility to specific viruses and bacteria. Since human endogenous retroviruses also encode Sags, these studies have broad implications for pathogen-induced responses in mice and humans.

【 授权许可】

CC BY