Studies of the Structure of Caprine Arthritis-Encephalitis Virus Surface Envelope Glycoprotein

We have isolated and sequenced a novel 11-kDa virucidal protein, named cyanovirin-N (CV-N), from cultures of the cyanobacterium (blue-green alga) Nostoc ellipsosporum. We also have produced CV-N recombinantly by expression of a corresponding DNA sequence in Escherichia coli. Low nanomolar concentrations of either natural or recombinant CV-N irreversibly inactivate diverse laboratory strains and primary isolates of human immunodeficiency virus (HIV) type 1 as well as strains of HIV type 2 and simian immunodeficiency virus. In addition, CV-N aborts cell-to-cell fusion and transmission of HIV-1 infection. Continuous, 2-day exposures of uninfected CEM-SS cells or peripheral blood lymphocytes to high concentrations (e.g., 9,000 nM) of CV-N were not lethal to these representative host cell types. The antiviral activity of CV-N is due, at least in part, to unique, high-affinity interactions of CV-N with the viral surface envelope glycoprotein gp120. The biological activity of CV-N is highly resistant to physicochemical denaturation, further enhancing its potential as an anti-HIV microbicide.

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Identification of a determinant within the human immunodeficiency virus 1 surface envelope glycoprotein critical for productive infection of primary monocytes.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.88.8.3097 ◽

1991 ◽

Vol 88 (8) ◽

pp. 3097-3101 ◽

Cited By ~ 138

Author(s):

P. Westervelt ◽

H. E. Gendelman ◽

L. Ratner

Keyword(s):

Human Immunodeficiency Virus ◽

Envelope Glycoprotein ◽

Productive Infection ◽

Surface Envelope Glycoprotein ◽

Immunodeficiency Virus ◽

Surface Envelope ◽

Human Immunodeficiency Virus 1

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Variability and Immunogenicity of Caprine Arthritis-Encephalitis Virus Surface Glycoprotein

Journal of Virology ◽

10.1128/jvi.74.13.6178-6185.2000 ◽

2000 ◽

Vol 74 (13) ◽

pp. 6178-6185 ◽

Cited By ~ 43

Author(s):

S. Valas ◽

C. Benoit ◽

C. Baudry ◽

G. Perrin ◽

R. Z. Mamoun

Keyword(s):

Phylogenetic Analyses ◽

Natural Infection ◽

Specific Antigen ◽

Encephalitis Virus ◽

Surface Glycoprotein ◽

Antigenic Determinants ◽

Virus Infections ◽

Virus Surface ◽

Caprine Arthritis Encephalitis Virus ◽

Variable Domains

ABSTRACT The complete surface glycoprotein (SU) nucleotide sequences of three French isolates of caprine arthritis-encephalitis virus (CAEV) were determined and compared with those of previously described isolates: three American isolates and one French isolate. Phylogenetic analyses revealed the existence of four distinct and roughly equidistant evolutionary CAEV subtypes. Four conserved and five variable domains were identified in the SU. The fine specificities of antibodies produced against these domains during natural infection were examined using a pepscan analysis. Nine immunogenic segments were delineated throughout the conserved and variable domains of SU, two of them corresponding to conserved immunodominant epitopes. Antigenic determinants which may be involved in the immunopathogenic process induced by CAEV were identified. These results also provide sensitive and specific antigen peptides for the serological detection and differentiation of CAEV and visna/maedi virus infections.

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Monoclonal Antibodies to Conformational Epitopes of the Surface Glycoprotein of Caprine Arthritis-Encephalitis Virus: Potential Application to Competitive-Inhibition Enzyme-Linked Immunosorbent Assay for Detecting Antibodies in Goat Sera

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.8.1.44-51.2001 ◽

2001 ◽

Vol 8 (1) ◽

pp. 44-51 ◽

Cited By ~ 18

Author(s):

Fuat Özyörük ◽

William P. Cheevers ◽

Gordon A. Hullinger ◽

Travis C. McGuire ◽

Melinda Hutton ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Immunosorbent Assay ◽

Competitive Inhibition ◽

Encephalitis Virus ◽

Surface Glycoprotein ◽

Enzyme Linked Immunosorbent Assay ◽

Western Blots ◽

Caprine Arthritis Encephalitis Virus ◽

Potential Applicability ◽

Surface Envelope

ABSTRACT Four immunoglobulin G1 monoclonal antibodies (MAbs) to the gp135 surface envelope glycoprotein (SU) of the 79–63 isolate of caprine arthritis-encephalitis virus (CAEV), referred to as CAEV-63, were characterized and evaluated for their ability to compete with antibody from CAEV-infected goats. Three murine MAbs (MAbs GPB16A, 29A, and 74A) and one caprine MAb (MAb F7-299) were examined. All MAbs reacted in nitrocellulose dot blots with native CAEV-63 SU purified by MAb F7-299 affinity chromatography, whereas none reacted with denatured and reduced SU. All MAbs reacted in Western blots with purified CAEV-63 SU or the SU component of whole-virus lysate following denaturation in the absence of reducing agent, indicating that intramolecular disulfide bonding was essential for epitope integrity. Peptide-N-glycosidase F digestion of SU abolished the reactivities of MAbs 74A and F7-299, whereas treatment of SU withN-acetylneuraminate glycohydrolase (sialidase A) under nonreducing conditions enhanced the reactivities of all MAbs as well as polyclonal goat sera. MAbs 29A and F7-299 were cross-reactive with the SU of an independent strain of CAEV (CAEV-Co). By enzyme-linked immunosorbent assay (ELISA), the reactivities of horseradish peroxidase (HRP)-conjugated MAbs 16A and 29A with homologous CAEV-63 SU were <10% of that of HRP-conjugated MAb 74A. The reactivity of HRP-conjugated MAb 74A was blocked by sera from goats immunized with CAEV-63 SU or infected with CAEV-63. The reactivity of MAb 74A was also blocked by sera from goats infected with a CAEV-Co molecular clone, although MAb 74A did not react with CAEV-Co SU in Western blots. Thus, goats infected with either CAEV-63 or CAEV-Co make antibodies that inhibit binding of MAb 74A to CAEV-63 SU. A competitive-inhibition ELISA based on displacement of MAb 74A reactivity has potential applicability for the serologic diagnosis of CAEV infection.

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Surface Envelope Glycoprotein Is B-Lymphocyte Immunodominant in Sheep Naturally Infected with Ovine Progressive Pneumonia Virus

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.12.6.797-800.2005 ◽

2005 ◽

Vol 12 (6) ◽

pp. 797-800 ◽

Cited By ~ 4

Author(s):

Lynn M. Herrmann ◽

Travis C. McGuire ◽

Isidro Hötzel ◽

Gregory S. Lewis ◽

Donald P. Knowles

Keyword(s):

Envelope Glycoprotein ◽

B Lymphocyte ◽

Serum Antibody ◽

Viral Proteins ◽

Infected Sheep ◽

Transmembrane Glycoprotein ◽

Immunodominant Antigen ◽

Surface Envelope Glycoprotein ◽

Surface Envelope ◽

Ovine Progressive Pneumonia

ABSTRACT The B-lymphocyte-immunodominant antigen involved in naturally ovine progressive pneumonia virus (OPPV)-infected mature sheep remains unknown. Therefore, the amount of antibody in sera from 10 naturally OPPV-infected sheep was evaluated by immunoprecipitation (IP) of the major viral proteins in [35S]methionine/cysteine-labeled OPPV (whole virus) lysate. Using an excess of OPPV proteins in whole-virus lysate, 8 out of 10 sheep had the highest serum antibody IP endpoint titers to the gp135 surface envelope glycoprotein (SU). Also, 2 out of 10 sheep had equivalent serum antibody IP endpoint titers to the transmembrane glycoprotein oligomer (TM90) and SU. Since these data indicate that SU is the immunodominant protein in most mature sheep persistently infected with OPPV, SU-specific diagnostic serological assays can be utilized for OPPV diagnosis.

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