Role of viral strains and host genes in determining levels of immune complexes in a model system: implications for HIV infection.
Virus-antibody immune complexes form during infection with most RNA and DNA viruses, including those with human immunodeficiency virus (HIV). Yet a subset of individuals so infected apparently does not mount such responses. To understand the principles involved, we studied the formation and deposition of virus-antibody immune complexes in the circulation in a model system utilizing mice persistently infected with lymphocytic choriomeningitis virus (LCMV). Although mice of several genetic haplotypes could be persistently infected with LCMV, mount anti-LCMV antibody responses, and form immune complexes levels varied among murine strains. Earlier, genetic analysis of high and low immune complex formers, their F1 crosses, and appropriately selected recombinant inbred strains located the ability to mount heightened immune responses in genes within the MHC. Further, variations among LCMV strains in the capacity to incite high levels of immune complex formation were found. Persistent infection with LCMV Armstrong (ARM) strain was associated with high levels of complexes in the circulation and marked deposits in the glomeruli of high-responder SWR/J mice. In contrast, persistent infection of SWR/J mice with LCMV Traub strain led to very low levels of circulating complexes and minimal immune complex deposition in tissues. The amount of virus carried during both infections was roughly equivalent indicating that the genetics of both the host and the virus play essential roles in whether or not immune complexes develop. Antibody responses in SWR/J mice persistently infected with LCMV ARM were 5- to 10-fold higher than responses of age- and sex-matched mice infected with LCMV Traub.(ABSTRACT TRUNCATED AT 250 WORDS)
Tishon
A
A
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA.
Salmi
A
A
Ahmed
R
R
Oldstone
M B
MB
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000032:analysis* / Q000097:blood; D000956:Antigens, Viral / Q000097:blood / Q000276:immunology; D015922:Complement C1q / Q000378:metabolism; D003433:Crosses, Genetic; D005796:Genes; D015658:HIV Infections / Q000276:immunology*; D007074:Immunoglobulin G / Q000032:analysis; D007678:Kidney Glomerulus / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains
D000914:Antibodies, Viral; D000936:Antigen-Antibody Complex; D000956:Antigens, Viral; D007074:Immunoglobulin G; D015922:Complement C1q