A single dominant locus restricts retrovirus replication in YBR/Ei mice

Area of Science:

• Immunology
• Genetics
• Virology

Background:

• Host genetic factors significantly influence viral infection outcomes.
• Studying retroviral resistance in humans is challenging; inbred mouse models offer a viable alternative.
• Mouse Mammary Tumor Virus (MMTV) is a mucosally transmitted retrovirus used to study host resistance.

Purpose of the Study:

• To identify and characterize the genetic mechanisms underlying resistance to MMTV infection in mice.
• To investigate the role of neonatal oral tolerance in retroviral resistance.
• To map the genetic locus responsible for MMTV resistance.

Main Methods:

• Utilized YBR/Ei mice, known to clear MMTV infection.
• Assessed the correlation between virus elimination and neonatal oral tolerance.
• Performed genetic mapping to identify the resistance locus.

Main Results:

• YBR/Ei mice eliminate MMTV, correlating with a lack of virus-specific neonatal oral tolerance.
• Resistance is independent of known antiviral mechanisms like neutralizing antibodies and cytotoxic T cells.
• A single, dominant genetic locus, provisionally named attenuation of virus titers (Avt), was identified on chromosome 18.

Conclusions:

• Neonatal oral tolerance is a critical mechanism that can suppress anti-retroviral immune responses.
• The identified Avt locus on chromosome 18 is a key determinant of MMTV resistance.
• Understanding these genetic resistance mechanisms is vital for human health and susceptibility to microbial infections.