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K V Holmes

Publications and source records attributed to K V Holmes.

At least 55 records · Page 3Linked to original sources
PubMed1993

Mouse hepatitis virus strain A59 and blocking antireceptor monoclonal antibody bind to the N-terminal domain of cellular receptor.

Mouse hepatitis virus (MHV) strain A59 uses as cellular receptors members of the carcinoembryonic antigen family in the immunoglobulin superfamily. Recombinant receptor proteins with deletions of whole or partial immunoglobulin domains were used to identify the regions of receptor glycoprotein recognized by virus and by antireceptor monoclonal antibody CC1, which blocks infection of murine cells. Monoclonal antibody CC1 and MHV-A59 virions bound only to recombinant proteins containing the entire first domain of MHV receptor. To determine which of the proteins could serve as functional virus receptors, receptor-negative hamster cells were transfected with recombinant deletion clones and then challenged with MHV-A59 virions. Receptor activity required the entire N-terminal domain with either the second or the fourth domain and the transmembrane and cytoplasmic domains. Recombinant proteins lacking the first domain or its C-terminal portion did not serve as viral receptors. Thus, like other virus receptors in the immunoglobulin superfamily, including CD4, poliovirus receptor, and intercellular adhesion molecule 1, the N-terminal domain of MHV receptor is recognized by the virus and the blocking monoclonal antibody.

Animals↗
PubMed1993

The Coronaviridae now comprises two genera, coronavirus and torovirus: report of the Coronaviridae Study Group.

At the April 1992, mid-term meeting of the International Committee on Taxonomy of Viruses (ICTV) a proposal from the Coronaviridae Study Group (CSG) to include the torovirus genus in the Coronaviridae was accepted. Following another proposal, the arterivirus genus was removed from the Togaviridae but not assigned to another family. The arteriviruses have some features in common with the Coronaviridae but also have major differences. After much debate, culminating in September 1992, it was decided that the CSG would not recommend inclusion of arterivirus in the Coronaviridae. It was agreed that (a) the nomenclature used for coronavirus genes, mRNAs and polypeptides (Cavanagh et al., 1990) should be used for toroviruses, (b) that the small (about 100 amino acids) membrane-associated protein, which is distinct from the integral membrane glycoprotein M, associated with virions of infectious bronchitis (Liu & Inglis, 1991) and transmissible gastroenteritis (Godet et al., 1992) coronaviruses would be referred to by the acronym sM (lower case 's') and (c) that 'pol' (polymerase) should be used as a working term for gene 1, which comprises open reading frames (ORFs) 1a and 1b in both genera of the Coronaviridae.

Arterivirus↗
PubMed1993

A common-source outbreak of callitrichid hepatitis in captive tamarins and marmosets.

Callitrichid hepatitis (CH) is a highly fatal, emerging arenavirus disease of captive South American marmosets and tamarins (Callitrichidae), including the endangered golden lion tamarin. A common-source outbreak of CH in golden lion tamarins and pygmy marmosets at a US zoo resulted from a single feeding of the primates with newborn mice in apparently infected with lymphocytic choriomeningitis virus (LCMV). Isolates from livers of mice and primates were related to isolates from previous CH outbreaks and to laboratory strains of LCMV by serology and nucleic acid hybridization, and 2 surviving animals developed antibody to other LCMVCH isolates and to laboratory strains of LCMV. Thus, LCMV, an arenavirus prevalent in wild mice in the US, can cause sporadic fatal hepatic disease in primates. Exposure of humans to wild or laboratory mice or to marmosets and tamarins that are infected with wild-type strains of LCMV poses the danger of serious disease.

Animals↗
PubMed1993

Several members of the mouse carcinoembryonic antigen-related glycoprotein family are functional receptors for the coronavirus mouse hepatitis virus-A59.

Mouse hepatitis virus-A59 (MHV-A59), a murine coronavirus, can utilize as a cellular receptor MHVR, a murine glycoprotein in the biliary glycoprotein (BGP) subfamily of the carcinoembryonic antigen (CEA) family in the immunoglobulin superfamily (G.S. Dveksler, M. N. Pensiero, C. B. Cardellichio, R. K. Williams, G.-S. Jiang, K. V. Holmes, and C. W. Dieffenbach, J. Virol. 65:6881-6891, 1991). Several different BGP isoforms are expressed in tissues of different mouse strains, and we have explored which of these glycoproteins can serve as functional receptors for MHV-A59. cDNA cloning, RNA-mediated polymerase chain reaction analysis, and Western immunoblotting with a monoclonal antibody, CC1, specific for the N-terminal domain of MHVR showed that the inbred mouse strains BALB/c, C3H, and C57BL/6 expressed transcripts and proteins of the MHVR isoform and/or its splice variants but not the mmCGM2 isoform. In contrast, adult SJL/J mice, which are resistant to infection with MHV-A59, express transcripts and proteins only of the mmCGM2-related isoforms, not MHVR. These data are compatible with the hypothesis that the MHVR and mmCGM2 glycoproteins may be encoded by different alleles of the same gene. We studied binding of anti-MHVR antibodies or MHV-A59 virions to proteins encoded by transcripts of MHVR and mmCGM2 and two splice variants of MHVR, one containing two immunoglobulin-like domains [MHVR(2d)] and the other with four domains as in MHVR but with a longer cytoplasmic domain [MHVR(4d)L]. We found that the three isoforms tested could serve as functional receptors for MHV-A59, although only isoforms that include the N-terminal domain of MHVR were recognized by monoclonal antibody CC1 in immunoblots or by MHV-A59 virions in virus overlay protein blot assays. Thus, in addition to MHVR, both the two-domain isoforms, mmCGM2 and MHVR(2d), and the MHVR(4d)L isoform served as functional virus receptors for MHV-A59. This is the first report of multiple related glycoprotein isoforms that can serve as functional receptors for a single enveloped virus.

3T3 Cells↗
PubMed1992

Human aminopeptidase N is a receptor for human coronavirus 229E.

Human coronaviruses (HCV) in two serogroups represented by HCV-229E and HCV-OC43 are an important cause of upper respiratory tract infections. Here we report that human aminopeptidase N, a cell-surface metalloprotease on intestinal, lung and kidney epithelial cells, is a receptor for human coronavirus strain HCV-229E, but not for HCV-OC43. A monoclonal antibody, RBS, blocked HCV-229E virus infection of human lung fibroblasts, immunoprecipitated aminopeptidase N and inhibited its enzymatic activity. HCV-229E-resistant murine fibroblasts became susceptible after transfection with complementary DNA encoding human aminopeptidase N. By contrast, infection of human cells with HCV-OC43 was not inhibited by antibody RBS and expression of aminopeptidase N did not enhance HCV-OC43 replication in mouse cells. A mutant aminopeptidase lacking the catalytic site of the enzyme did not bind HCV-229E or RBS and did not render murine cells susceptible to HCV-229E infection, suggesting that the virus-binding site may lie at or near the active site of the human aminopeptidase molecule.

Aminopeptidases↗
PubMed1992

Prevalence of serum antibodies against lymphocytic choriomeningitis virus in selected populations from two U.S. cities.

An ELISA was developed for measuring serum antibodies against the arenavirus lymphocytic choriomeningitis virus (LCMV) and a closely related isolate termed callitrichid hepatitis virus (CHV). The ELISA was used to test sera from healthy adults and from hepatitis patients. In Birmingham, Alabama, the seropositivity rate for healthy black women was 5.1% (7/138), and the rate for patients with all types of hepatitis or cirrhosis was 4.3% (2/46). In San Antonio, Texas, the seropositivity rate among a clinical series of patients with non-A, non-B hepatitis was 0 (0/20), and the rate among persons rejected from blood donation because of high serum alanine aminotransferase levels was 2.4% (2/82). These results indicate that infection with LCMV or CHV is common in Birmingham but that infection is not associated with hepatitis.

Adult↗
PubMed1992

Coronavirus species specificity: murine coronavirus binds to a mouse-specific epitope on its carcinoembryonic antigen-related receptor glycoprotein.

Like most coronaviruses, the coronavirus mouse hepatitis virus (MHV) exhibits strong species specificity, causing natural infection only in mice. MHV-A59 virions use as a receptor a 110- to 120-kDa glycoprotein (MHVR) in the carcinoembryonic antigen (CEA) family of glycoproteins (G. S. Dveksler, M. N. Pensiero, C. B. Cardellichio, R. K. Williams, G. S. Jiang, K. V. Holmes, and C. W. Dieffenbach, J. Virol. 65:6881-6891, 1991; and R. K. Williams, G. S. Jiang, and K. V. Holmes, Proc. Natl. Acad. Sci. USA 88:5533-5536, 1991). The role of virus-receptor interactions in determining the species specificity of MHV-A59 was examined by comparing the binding of virus and antireceptor antibodies to cell lines and intestinal brush border membranes (BBM) from many species. Polyclonal antireceptor antiserum (anti-MHVR) raised by immunization of SJL/J mice with BALB/c BBM recognized MHVR specifically in immunoblots of BALB/c BBM but not in BBM from adult SJL/J mice that are resistant to infection with MHV-A59, indicating a major difference in epitopes between MHVR and its SJL/J homolog which does not bind MHV (7). Anti-MHVR bound to plasma membranes of MHV-susceptible murine cell lines but not to membranes of human, cat, dog, monkey, or hamster cell lines. Cell lines from these species were resistant to MHV-A59 infection, and only the murine cell lines tested were susceptible. Pretreatment of murine fibroblasts with anti-MHVR prevented binding of radiolabeled virions to murine cells and prevented virus infection. Solid-phase virus-binding assays and virus overlay protein blot assays showed that MHV-A59 virions bound to MHVR on intestinal BBM from MHV-susceptible mouse strains but not to proteins on intestinal BBM from humans, cats, dogs, pigs, cows, rabbits, rats, cotton rats, or chickens. In immunoblots of BBM from these species, both polyclonal and monoclonal antireceptor antibodies that block MHV-A59 infection of murine cells recognized only the murine CEA-related glycoprotein and not homologous CEA-related glycoproteins of other species. These results suggest that MHV-A59 binds to a mouse-specific epitope of MHVR, and they support the hypothesis that the species specificity of MHV-A59 infection may be due to the specificity of the virus-receptor interaction.

3T3 Cells↗
PubMed1992

Binding of the coronavirus mouse hepatitis virus A59 to its receptor expressed from a recombinant vaccinia virus depends on posttranslational processing of the receptor glycoprotein.

Recently, we showed that a murine member of the carcinoembryonic antigen family of glycoproteins serves as a cellular receptor (MHVR) for the coronavirus mouse hepatitis virus A59 (MHV-A59) (G. S. Dveksler, M. N. Pensiero, C. B. Cardellichio, R. K. Williams, G.-S. Jiang, K. V. Holmes, and C. W. Dieffenbach, J. Virol. 65:6881-6891, 1991; R. K. Williams, G.-S. Jiang, and K. V. Holmes, Proc. Natl. Acad. Sci. USA 88:5533-5536, 1991). To examine the role of posttranscriptional modification of MHVR on virus-receptor interactions, a vaccinia virus-based expression system was employed. Expression from the vaccinia virus recombinant (Vac-MHVR) in BHK-21 cells resulted in high levels of MHVR glycoprotein on the cell surface and made these cells susceptible to MHV-A59 infection. Nonglycosylated core MHVR proteins were made in Vac-MHVR-infected BHK-21 cells in the presence of tunicamycin by in vitro translation of MHVR mRNA in a rabbit reticulocyte cell-free system in the absence of microsomal membranes and by expression of an N-terminal deletion clone of MHVR lacking its signal peptide. These three nonglycosylated MHVR proteins were recognized by polyclonal antibody against affinity-purified receptor but did not bind antireceptor monoclonal antibody (MAb) CC1 or MHV-A59 virions. Partial glycosylation of MHVR, either expressed in Vac-MHVR-infected cells treated with monensin or synthesized by in vitro translation with microsomal membranes, restored both the MAb CC1- and the virus-binding activities of the MHVR glycoprotein. Deletion of 26 amino acids at the carboxyl terminus of MHVR resulted in a secreted protein which was able to bind MAb CC1 and MHV-A59. These results suggest that either a carbohydrate moiety is an element of the MHVR-binding site(s) for virus and MAb CC1 or a posttranslational membrane-associated process is required for functional conformation of the receptor glycoprotein.

Amino Acid Sequence↗
PubMed1991

Receptor for mouse hepatitis virus is a member of the carcinoembryonic antigen family of glycoproteins.

The receptor for mouse hepatitis virus (MHV), a murine coronavirus, is a 110- to 120-kDa glycoprotein on intestinal brush border membranes and hepatocyte membranes. The N-terminal 25-amino acid sequence of immunoaffinity-purified MHV receptor was identical to the predicted mature N termini of two mouse genes related to human carcinoembryonic antigen (CEA) and was strongly homologous to the N termini of members of the CEA family in humans and rats. Polyclonal antibodies to human CEA recognized the immunoaffinity-purified MHV receptor and the MHV receptor in liver membranes and intestinal brush border membranes from MHV-susceptible mouse strains. In membranes from MHV-resistant SJL/J mice, the anti-CEA antibodies recognized a homologous glycoprotein that failed to bind MHV. The MHV receptor glycoprotein was detected in membranes of BALB/c colon, small intestine, and liver, which are the principal targets for MHV replication in vivo. The MHV receptor glycoprotein resembled members of the human CEA family in molecular weight, acidic pI, extensive glycosylation, solubility in perchloric acid, and tissue distribution. Thus, the MHV receptor is, to our knowledge, the first member of the CEA family of glycoproteins to be identified as a virus receptor.

Amino Acid Sequence↗
PubMed1991

Monoclonal antibody to the receptor for murine coronavirus MHV-A59 inhibits viral replication in vivo.

Because many strains of mouse hepatitis virus (MHV) infect laboratory mice, no effective vaccine has yet been developed. An alternative approach to control MHV disease is the use of a host cell receptor-targeted ligand. To address the potential usefulness of this approach, a monoclonal antibody directed against the host cell receptor for the coronavirus MHV-A59 was administered to infant mice that were then challenged oronasally with 10(4) intracerebral infant mouse median lethal doses of MHV-A59. Antibody treatment of virus-challenged mice resulted in lower proportions of mice with MHV-A59 in target organs and markedly reduced viral titers in these organs compared with mock-treated infected mice. Some antibody-treated infected mice survived for 7 days after viral challenge, whereas no mock-treated, infected mice survived beyond day 3 after viral inoculation. These results support a receptor-targeted approach to intervention in coronavirus disease.

Animals↗
PubMed1991

Cloning of the mouse hepatitis virus (MHV) receptor: expression in human and hamster cell lines confers susceptibility to MHV.

The cellular receptor for murine coronavirus mouse hepatitis virus (MHV)-A59 is a member of the carcinoembryonic antigen (CEA) family of glycoproteins in the immunoglobulin superfamily. We isolated a cDNA clone (MHVR1) encoding the MHV receptor. The sequence of this clone predicts a 424-amino-acid glycoprotein with four immunoglobulinlike domains, a transmembrane domain, and a short intracytoplasmic tail, MHVR1 is closely related to the murine CEA-related clone mmCGM1 (Mus musculus carcinoembryonic antigen gene family member). Western blot (immunoblot) analysis performed with antireceptor antibodies detected a glycoprotein of 120 kDa in BHK cells stably transfected with MHVR1. This corresponds to the size of the MHV receptor expressed in mouse intestine and liver. Human and hamster fibroblasts transfected with MHVR1 became susceptible to infection with MHV-A59. Like MHV-susceptible mouse fibroblasts, the MHVR1-transfected human and hamster cells were protected from MHV infection by pretreatment with monoclonal antireceptor antibody CC1. Thus, the 110- to 120-kDa CEA-related glycoprotein encoded by MHVR1 is a functional receptor for murine coronavirus MHV-A59.

Amino Acid Sequence↗
PubMed1991

Isolation of an arenavirus from a marmoset with callitrichid hepatitis and its serologic association with disease.

Callitrichid hepatitis (CH) is an acute, often fatal viral infection of New World primates from the family Callitrichidae. The etiologic agent of CH is unknown. We report here the isolation of an arenavirus from a common marmoset (Callithrix jacchus) with CH by using in vitro cultures of marmoset hepatocytes and Vero-E6 cells. Enveloped virions 67 to 133 nm in diameter with ribosomelike internal structures were seen in infected cultures. Immunofluorescence and Western immunoblot analysis using CH-specific antisera (principally from animals exposed to CH during zoo outbreaks) revealed three antigens in cells infected with this CH-associated virus (CHV). These antigens had the same electrophoretic mobilities on sodium dodecyl sulfate-polyacrylamide gels as did the nucleocapsid, GP2, and GPC proteins of lymphocytic choriomeningitis virus (LCMV). Monoclonal antibodies specific for these arenavirus proteins also reacted with the three CHV antigens. Conversely, the CH-specific antisera reacted with the nucleocapsid, GP2, and GPC proteins of LCMV. CHV thus appears to be a close antigenic relative of LCMV. The serologic association of CHV with several CH outbreaks implicate it as the etiologic agent of this disease.

Animals↗
PubMed1990

MHV-resistant SJL/J mice express a non-functional homolog to the MHV receptor glycoprotein.

MHV-A59 recognizes a 100-110 K glycoprotein receptor on intestinal and liver plasma membranes. The receptor protein was affinity purified using an anti-receptor monoclonal antibody. Purified receptor was sequenced from the 1st to the 15th amino acids. Antiserum raised against a synthetic peptide having this sequence bound to the 110 K receptor from BALB/c intestine and a 58 K fragment of the receptor. SJL/J mice are resistant to MHV-A59 and their plasma membranes were previously shown to lack binding to MHV. However, anti-peptide antibody bound to a 105 K protein and a 53 K protein fragment from SJL/J plasma membranes. These SJL/J proteins did not bind MHV or to the blocking monoclonal anti-receptor antibody. Genetic resistance of SJL/J mice to MHV-A59 appears to be due to mutation of the receptor glycoprotein resulting in a molecule that does not bind MHV.

Animals↗