Antibody responses to murine cytomegalovirus in genetically resistant and susceptible strains of mice.

Abstract

The role of antibodies as mediators of genetically determined resistance to murine cytomegalovirus (MCMV) in mice has not been elucidated. The ability of mice with different MCMV resistance phenotypes to produce an antibody response to MCMV was investigated in order to assess whether the host genotypes that control resistance also influence antibody production. Antibodies to MCMV in the sera of resistant (BALB.K, CBA/CaH, B10.BR) and susceptible [BALB/c, BALB.B, C57BL/10ScSn (B10), B10.D2, B10.A, A/J] mice were determined by ELISA and/or a complement-requiring neutralization assay. IgM antibodies were produced by all strains of mice as early as 3 to 5 days post-infection (p.i.) with maximum titres observed after 10 days p.i. for some strains, whilst IgG antibodies were produced by 5 to 7 days p.i. with maximum titres at 20 days p.i. IgA antibodies were not detected in the sera of MCMV-infected mice. Virulent MCMV induced higher antibody titres than either attenuated or u.v.-inactivated forms of the virus. Although high doses of virulent virus delayed the early production of IgM antibody they did not adversely affect the kinetics of IgG antibody production. High titres of neutralizing antibodies were detected as early as day 3 post-inoculation of virulent virus; when attenuated virus was used in the neutralization assay, this was found to be more easily neutralized than salivary gland-derived virus. Interestingly, although guinea-pig complement greatly enhanced antibody-mediated neutralization of MCMV, mouse complement was also effective at enhancing neutralization. Although genetically determined resistance to MCMV is an early event with the resistant phenotype being demonstrable during the first few days of the infection, there was no evidence that antibodies were responsible for this resistance since neither antibody titres nor the time of first appearance of antibody correlated with resistance status. However, these results do not exclude a more general role for antibody in limiting MCMV infection, especially in immunity to re-infection since passively transferred antibodies from resistant or susceptible mouse strains lowered virus titres in MCMV-infected animals.