Year: 2005
Type: dissertation
Abstract: Mouse mammary tumor virus (MMTV) is an oncogenic retrovirus that \ncauses mammary tumors in susceptible mice within 6 to 9 months of infection. \nType B leukemogenic virus (TBLV) is a variant of MMTV that induces thymic \nlymphomas in mice, instead of mammary tumors, with a shorter latency. Exogenous \nMMTV has a complicated life cycle involving milk-borne virus transmission and \ntissue type and differentiation-specific regulation of viral transcription. Most inbred \nmouse strains also harbor endogenous MMTV proviruses (Mtvs) in their germline \nthat are inherited according to Mendelian rules and are usually not associated with \nmammary tumorigenesis. \nThis thesis reports studies on the intricate relationship of MMTV with \nits host by demonstrating that the outcome of MMTV infection is influenced \nby both the composition of viral transcriptional elements and by host genetics. \nThis is the first demonstration that the absence of negative regulation of viral \ntranscription and presence of a T-cell specific enhancer in lymphoid cells converts \na mammotropic MMTV to a lymphotropic virus. Interestingly, the endogenous \nMtv loci in the BALB/cJ mouse genome are required for susceptibility to infection \nand tumorigenesis by both MMTV and TBLV. A BALB/cJ congenic mouse strain \nlacking endogenous Mtvs (BALB/Mtv-null) is highly resistant to both MMTV \nand TBLV. The resistance is not mediated by the production of MMTV-specific \nneutralizing antibodies in the BALB/Mtv-null strain. However, cell-mediated \nimmune response directed against MMTV-infected cells might contribute towards \nthe tumor resistance phenotype. The BALB/Mtv-null mice also are resistant to \noral infection with the bacterial pathogen Vibrio cholerae compared to BALB/cJ \nmice, and this resistance to V. cholerae correlates with the absence of endogenous \nMtvs. Thus, the BALB/Mtv-null mice demonstrate a novel mode of resistance to \nmultiple pathogens that appears to be linked to expression of MMTV genes. These \ndata support a role for endogenous Mtvs in determining susceptibility to multiple \npathogens.
Author: Sanchita Bhadra
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1958130372