B lymphocyte activation by coinfection prevents immune control of friend virus infection

Area of Science:

• Immunology
• Virology
• Retroviral Infections

Background:

• Adaptive immunity typically fails to eliminate retroviral infections but controls viral replication and prevents disease.
• Friend virus (FV) causes persistent infection and leukemia in mice, influenced by genetic and extrinsic factors.
• Coinfection can significantly alter the course of viral diseases.

Purpose of the Study:

• To investigate the impact of coinfection on immune control requirements for Friend virus (FV) infection.
• To determine how lactate dehydrogenase-elevating virus (LDV) coinfection affects FV-induced disease.
• To elucidate the mechanisms by which LDV coinfection enhances FV pathogenicity.

Main Methods:

• Congenic C57BL/6 mice with a Friend virus susceptibility 2 gene allele were used.
• Mice were infected with FV alone or coinfected with FV and LDV.
• T cell- and antibody (Ab)-dependent immune responses were assessed.
• Neutralizing antibody induction and B cell repertoire activation were analyzed.

Main Results:

• Congenic mice resisted FV infection through T cell- and Ab-dependent immunity.
• LDV coinfection rendered these mice highly susceptible to FV infection and leukemia.
• LDV delayed FV-specific neutralizing antibody induction and counteracted protective adaptive immunity.
• The disease-enhancing effect of LDV required a polyclonal B cell repertoire and was mimicked by direct B cell activation.

Conclusions:

• Coinfection with LDV severely compromises immune control of FV infection.
• LDV coinfection delays adaptive immune responses, including antibody production.
• Immune activation by coinfecting agents can exacerbate retroviral pathogenicity.
• Polyclonal B cell activation plays a critical role in LDV-mediated enhancement of FV disease.