Modification by Adoptive Humoral Immunity of Murine Cytomegalovirus Infection

Abstract

The effects of specific antiviral antibody on several aspects of infection with murine cytomegalovirus (CMV) were examined. Administration of immune serum 24 hr before subcutaneous inoculation of 10(5) plaque-forming units of murine CMV prevented detectable viral replication in the tissues of 92% of animals. Protection was associated with the immune globulin fraction and not with normal serum or heterologous antiviral serum. However, the development of latent murine CMV infection was not prevented by prior administration of antibody since immunosuppression with antilymphocyte serum and cortisone 16 weeks later unmasked dormant virus in 17 of 20 animals. In normal animals murine CMV-immune serum administered six days after acute virus infection had been initiated did not influence the outcome; however, in immunosuppressed mice, virus dissemination during acute infection was substantially reduced by specific antibody. These results demonstrate a significant effect of humoral immunity on the course of experimental CMV infection.

A flow cytometry-based method for detecting antibody responses to murine cytomegalovirus infection

“…Previously the most sensitive described technique to detect MCMV antibody response after infection has been ELISA. Our ELISA results are consistent with those published by others (Shanley et al, 1981), and suggest that ELISA should remain the "gold standard" for absolute sensitivity. Unfortunately, there is some controversy with this technique possibly being overly sensitive.…”

“…ELISA analysis allowed detection at dilutions up to 1:320, becoming indistinguishable from negative controls beyond that ( Figure 5B). These results are similar to ELISA results from other investigators (Shanley et al, 1981). A dilution of 1:20 for positive controls consistently gave 93-98% target cell binding and was thus chosen for all subsequent studies.…”

“…Adoptive transfer of anti-CMV antibody has been shown to be protective during acute infection (Araullo-Cruz et al, 1978;Farrell and Shellam, 1991;Lawson et al, 1988;Shanley et al, 1981), but does not prevent development of latent infection (Shanley et al, 1981). Although preformed antibody does help protect from lethal primary infection, it is not required for viral control in non-lethal models, but does appear to be important in viral control after reactivation from latency (Jonjic et al, 1994).…”

“…If these hypotheses are true, then one could conclude from our results that humoral responses are important in viral control during acute infection in BALB/c mice. Passive immunization studies have shown reduction in mortality when a lethal dose of MCMV was given (Araullo-Cruz et al, 1978;Farrell and Shellam, 1991;Lawson et al, 1988;Shanley et al, 1981), but there are no data that we are aware of directly studying the importance of antibody responses in viral control in the BALB/c strain. Work by Jonic et al using B-cell deficient mice clearly supports the hypothesis that humoral responses are dispensable during primary MCMV infection (Jonjic et al, 1994), but B-cell knockout mice used in these studies had a C57BL/6 background.…”

Characterization of neutralizing monoclonal antibodies to murine cytomegalovirus

“…In both the human and murine host, CMV infection elicits antibodies that possess neutralizing activity in vitro (Stalder & Ehrensberger, 1980;Lawson et al, 1988) and reduce the severity of CMV-induced disease when passively administered in vivo, particularly in the immunocompromised host (Araullo-Cruz et al, 1978;Shanley et al, 1981 ;Winston et al, 1987). As considerable heterogeneity in the recognition of HCMV proteins by different human sera has been observed Landini & Michelson (1988), the murine model has proved useful for the analysis of viral proteins recognized during seroconversion and for studying the parameters that may contribute to the heterogeneous response in man.…”