Impaired T and B cell subpopulations involved in a chronic disease induced by mouse hepatitis virus type 3.

A chronic viral infection can occur when the host immune system fails to detect the viruses. Mouse hepatitis virus type 3 (MHV3) seems to be an excellent model for the study of the relationship between viral-induced immunodeficiency and the development of chronic disease. Animals that survive acute hepatitis develop a chronic disease characterized by viral persistency in various organs, including the brain, spleen, and thymus, and they eventually die within the next 3 mo postinfection (p.i.). To verify whether T and B cell immunodeficiency occurs either in the acute or chronic phase of the disease, the percentage and absolute number of splenic T and B lymphocytes, thymic T, or bone marrow B-lineage cell subpopulations were recorded at various times p.i. in pathogenic L2-MHV3-infected and nonpathogenic YAC-MHV3-infected (C57BL/6 x A/J) F1 mice. Splenic T and B cells were depleted as early as 48 h p.i., and maintained at low levels for up to 3 mo until death of mice. Such depletions resulted from thymic depletion in all T cell subpopulations, and in B (cytoplasmic micro-chain+ and surface micro-chain+) lymphocytes only in the bone marrow of pathogenic L2-MHV3-infected mice. In vitro studies of purified thymic stromal cells have produced a nonproductive L2-MHV3 replication with a low viral transmission to complexed thymocytes. However, pre-B and B cells have supported a productive viral replication, generating abnormal forms, which leads to cell lysis. These results are discussed in relation to viral persistency in the brain and lymphoid cells, which results from a chronic impairment of cellular and humoral immune mechanisms that are involved in the viral elimination process.