Abstract
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.
Highlights
Pathogens are recognized by the immune system, which has been divided into innate and adaptive responses
N1 mice were screened for the absence of endogenous Mtvs using PCR from tail-derived genomic DNA, and Mtv-free progeny were mated to BALB/c mice
The absence of endogenous Mtvs was verified by PCR analysis of mouse genomic DNA using primers specific for each of the three endogenous mammary tumor virus (MMTV) proviruses of BALB/c mice, Mtv6, 8, and 9 (Figure 1A)
Summary
Pathogens are recognized by the immune system, which has been divided into innate and adaptive responses. Innate immunity detects pathogen-associated molecular patterns (PAMPs) on the invading organisms [1]. PAMPs interact with pattern recognition receptors, which often contain a cytosolic region called the Toll/IL-1 receptor domain [2]. Signaling through the Toll/IL-1 receptor domains leads to activation of inflammatory responses and initiation of adaptive immunity [4]. Another form of innate immunity ( known as intrinsic immunity) appears as non-inducible barriers to pathogen replication as exemplified by apolipoprotein B mRNA-editing enzyme catalytic polypeptides, which lead to the degradation or mutation of viral genomes [5]. Adaptive immunity provides an antigen-specific response that can evolve and provide immunological memory [4]
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