Protective effect of monoclonal antibodies on lethal mouse hepatitis virus infection in mice

Abstract

Neutralizing and nonneutralizing monoclonal antibodies to the peplomer glycoprotein and nucleocapsid protein of a mouse hepatitis virus (MHV), MHV-NuU, protected mice against lethal MHV-2 challenge. Histopathologically, livers of mice receiving protective antibodies showed some focal necrotic lesions with remarkable cellular infitration instead of fulminant hepatitis caused by MHV-2. Mouse hepatitis virus (MHV) is a member of the coronavirus group producing both acute and chronic diseases in various species of animals (15, 17, 25). Most MHV strains have been shown to have the nucleocapsid protein (NP) and the minor (El) and major (E2) envelope glycoproteins (18, 19). El is probably of the viral matrix, whereas E2 forms the peplomers that have important roles in attachment to host cells (18, 19). We described previously the production of monoclonal antibodies (MAbs) to low-virulence MHV-NuU, an isolate from a wasted nude mouse (7), and their specificity for viral polypeptides (10). Those MAbs were shown to be crossreactive in vitro with other strains of MHV including the highly hepatitogenic strain MHV-2 (6, 11, 12). This paper describes protective effects of MAbs against E2 as well as NP of MHV-NuU in highly virulent MHV-2 infection in mice.

The antiviral activity of antibodies in vitro and in vivo

“…Monitoring of the viral load in liver, spleen, and brain allowed the effects of mAbs in i.v. challenge of mice with MHV-2 to be explored quantitatively (Nakanaga et al, 1986). Protection against lethal challenge was provided by a potent neutralizing anti-E2 mAb, a nonneutralizing anti-E2 mAb, and a nonneutralizing anti-nucleoprotein (NP) mAb.…”

Mouse hepatitis virus nucleocapsid protein-specific cytotoxic T lymphocytes are Ld restricted and specific for the carboxy terminus

“…To begin to understand the role of the viral proteins in the anti-JHMV CTL response, recombinant vaccinia viruses were constructed which express the JHMV nucleocapsid (N) protein and a series of deletions from the carboxy terminus. The N protein was chosen because it is the major virus protein synthesized in infected cells (Spaan et a/., 1988;Lai, 1990), it is a highly conserved protein (Parker and Masters, 1990), mAb specific for the N protein can protect mice from MHV infection (Nakanaga et al, 1986;Lecomte et al, 1987;Stohlman, unpublished), and expression of the N protein is used as a marker for chronic CNS infection (Erlich et a/., 1987(Erlich et a/., , 1989Perlman and Ries, 1987). Our data demonstrate that JHMV elicits an anti-N protein CTL response in Balb/c (H-Zd) mice, that the only detectable epitope of the N protein resides within carboxy-terminal amino acids 306 to 455, and that the N-specific CTL response is restricted to the Ld Class 1 molecule.…”

Immune response to a murine coronavirus: Identification of a homing receptor-negative CD4+ T cell subset that responds to viral glycoproteins

“…Both humoral and cellular immunity protect mice from the acute, fatal encephalitis caused by the neurotropic JHM strain of MHV (MHV-JHM). The acute MHV-JHM infection can be prevented by infusion of monoclonal antibodies directed against the surface glycoprotein (S), the transmembrane glycoprotein (M), or the nucleocapsid protein (N) Nakanaga et al, 1986;Lecomte et a/., 1987;Fleming et al, 1989). Suckling mice are protected from the acute disease if they are nursed by dams previously immunized against MHV-JHM (Pickel eta/., 1985;Perlman et a/., 1987a).…”