scholarly journals Specificity of serum neutralizing antibodies induced by transient immune suppression of inapparent carrier ponies infected with a neutralization-resistant equine infectious anemia virus envelope strain

2005 ◽  
Vol 86 (1) ◽  
pp. 139-149 ◽  
Author(s):  
Laryssa Howe ◽  
Jodi K. Craigo ◽  
Charles J. Issel ◽  
Ronald C. Montelaro
Keyword(s):  
Immune Suppression ◽  
Neutralizing Antibodies ◽  
Equine Infectious Anemia Virus ◽  
Antibody Responses ◽  
Serum Antibodies ◽  
Virus Envelope ◽  
Specific Serum ◽  
Surface Envelope ◽  
Equine Infectious Anemia ◽  
Anemia Virus

It has been previously reported that transient corticosteroid immune suppression of ponies experimentally infected with a highly neutralization resistant envelope variant of equine infectious anemia virus (EIAV), designated EIAVΔPND, resulted in the appearance of type-specific serum antibodies to the infecting EIAVΔPND virus. The current study was designed to determine if this induction of serum neutralizing antibodies was associated with changes in the specificity of envelope determinants targeted by serum antibodies or caused by changes in the nature of the antibodies targeted to previously defined surface envelope gp90 V3 and V4 neutralization determinants. To address this question, the envelope determinants of neutralization by post-immune suppression serum were mapped. The results demonstrated that the neutralization sensitivity to post-immune suppression serum antibodies mapped specifically to the surface envelope gp90 V3 and V4 domains, individually or in combination. Thus, these data indicate that the development of serum neutralizing antibodies to the resistant EIAVΔPND was due to an enhancement of host antibody responses caused by transient immune suppression and the associated increase in virus replication.

scholarly journals Mapping of Equine Lentivirus Receptor 1 Residues Critical for Equine Infectious Anemia Virus Envelope Binding

2007 ◽  
Vol 82 (3) ◽  
pp. 1204-1213 ◽  
Author(s):  
Baoshan Zhang ◽  
Chengqun Sun ◽  
Sha Jin ◽  
Michael Cascio ◽  
Ronald C. Montelaro
Keyword(s):  
Equine Infectious Anemia Virus ◽  
Tumor Necrosis Factor Receptor ◽  
Binding Domain ◽  
Virus Envelope ◽  
Immunodeficiency Virus ◽  
Equine Infectious Anemia ◽  
Anemia Virus ◽  
Functional Receptor ◽  
Herpesvirus Entry Mediator ◽  
Necrosis Factor

ABSTRACT The equine lentivirus receptor 1 (ELR1), a member of the tumor necrosis factor receptor (TNFR) protein family, has been identified as a functional receptor for equine infectious anemia virus (EIAV). Toward defining the functional interactions between the EIAV SU protein (gp90) and its ELR1 receptor, we mapped the gp90 binding domain of ELR1 by a combination of binding and functional assays using the EIAV SU gp90 protein and various chimeric receptor proteins derived from exchanges between the functional ELR1 and the nonbinding homolog, mouse herpesvirus entry mediator (murine HveA). Complementary exchanges of the respective cysteine-rich domains (CRD) between the ELR1 and murine HveA proteins revealed CRD1 as the predominant determinant of functional gp90 binding to ELR1 and also to a chimeric murine HveA protein expressed on the surface of transfected Cf2Th cells. Mutations of individual amino acids in the CRD1 segment of ELR1 and murine HveA indicated the Leu70 in CRD1 as essential for functional binding of EIAV gp90 and for virus infection of transduced Cf2Th cells. The specificity of the EIAV SU binding domain identified for the ELR1 receptor is fundamentally identical to that reported previously for functional binding of feline immunodeficiency virus SU to its coreceptor CD134, another TNFR protein. These results indicate unexpected common features of the specific mechanisms by which diverse lentiviruses can employ TNFR proteins as functional receptors.

scholarly journals Antibody Escape Kinetics of Equine Infectious Anemia Virus Infection of Horses

2015 ◽  
Vol 89 (13) ◽  
pp. 6945-6951 ◽  
Author(s):  
Elissa J. Schwartz ◽  
Seema Nanda ◽  
Robert H. Mealey
Keyword(s):  
Neutralizing Antibodies ◽  
Equine Infectious Anemia Virus ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Fitness Costs ◽  
Equine Infectious Anemia ◽  
Anemia Virus ◽  
Kinetics Of ◽  
Virus Fitness

Lentivirus escape from neutralizing antibodies (NAbs) is not well understood. In this work, we quantified antibody escape of a lentivirus, using antibody escape data from horses infected with equine infectious anemia virus. We calculated antibody blocking rates of wild-type virus, fitness costs of mutant virus, and growth rates of both viruses. These quantitative kinetic estimates of antibody escape are important for understanding lentiviral control by antibody neutralization and in developing NAb-eliciting vaccine strategies.

scholarly journals Selection of a Rare Neutralization-Resistant Variant following Passive Transfer of Convalescent Immune Plasma in Equine Infectious Anemia Virus-Challenged SCID Horses

2010 ◽  
Vol 84 (13) ◽  
pp. 6536-6548 ◽  
Author(s):  
Sandra D. Taylor ◽  
Steven R. Leib ◽  
Susan Carpenter ◽  
Robert H. Mealey
Keyword(s):  
Neutralizing Antibodies ◽  
Equine Infectious Anemia Virus ◽  
Severe Combined Immunodeficiency ◽  
Febrile Episode ◽  
Clinical Disease ◽  
Resistant Variant ◽  
Homologous Virus ◽  
Equine Infectious Anemia ◽  
Anemia Virus

ABSTRACT Vaccines preventing HIV-1 infection will likely elicit antibodies that neutralize diverse strains. However, the capacity for lentiviruses to escape broadly neutralizing antibodies (NAbs) is not completely understood, nor is it known whether NAbs alone can control heterologous infection. Here, we determined that convalescent immune plasma from a horse persistently infected with equine infectious anemia virus (EIAV) neutralized homologous virus and several envelope variants containing heterologous principal neutralizing domains (PND). Plasma was infused into young horses (foals) affected with severe combined immunodeficiency (SCID), followed by challenge with a homologous EIAV stock. Treated SCID foals were protected against clinical disease, with complete prevention of infection occurring in one foal. In three SCID foals, a novel neutralization-resistant variant arose that was found to preexist at a low frequency in the challenge inoculum. In contrast, SCID foals infused with nonimmune plasma developed acute disease associated with high levels of the predominant challenge virus. Following transfer to an immunocompetent horse, the neutralization-resistant variant induced a single febrile episode and was subsequently controlled in the absence of type-specific NAb. Long-term control was associated with the presence of cytotoxic T lymphocytes (CTL). Our results demonstrate that immune plasma with neutralizing activity against heterologous PND variants can prevent lentivirus infection and clinical disease in the complete absence of T cells. Importantly, however, rare neutralization-resistant envelope variants can replicate in vivo under relatively broad selection pressure, highlighting the need for protective lentivirus vaccines to elicit NAb responses with increased breadth and potency and/or CTL that target conserved epitopes.

scholarly journals Serological Method Using Recombinant S2 Protein To Differentiate Equine Infectious Anemia Virus (EIAV)-Infected and EIAV-Vaccinated Horses

2004 ◽  
Vol 11 (6) ◽  
pp. 1120-1129 ◽  
Author(s):  
Sha Jin ◽  
Charles J. Issel ◽  
Ronald C. Montelaro
Keyword(s):  
Vaccine Strain ◽  
Equine Infectious Anemia Virus ◽  
Genetically Engineered ◽  
Commercial Application ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Antibodies ◽  
Serological Method ◽  
Live Virus ◽  
Equine Infectious Anemia ◽  
Anemia Virus

ABSTRACT We recently reported a highly protective attenuated live virus vaccine for equine infectious anemia virus (EIAV) based on a proviral construct (EIAVUKΔS2) with a genetically engineered mutation in the viral S2 gene that eliminates expression of this accessory protein. While the EIAVUKΔS2 vaccine provides protection from detectable infection by experimental challenge with highly virulent virus, the potential for commercial application of this vaccine is complicated by the fact that horses inoculated with the EIAVUKΔS2 vaccine strain become seropositive in various reference diagnostic assays based on detection of antibodies to virion core or envelope proteins. To address this issue, we describe here the development and optimization of a new serologic EIAV diagnostic enzyme-linked immunosorbent assay (ELISA) to detect serum antibodies to the EIAV S2 protein that are produced in infected horses but not in horses inoculated with the EIAVUKΔS2 vaccine virus. The test S2 protein antigen was developed using the S2 gene sequence from the EIAVUK strain of virus and a series of modifications to facilitate production and purification of the diagnostic antigen, designated HS2G. Using this HS2G as antigen, we describe the development of an affinity ELISA that provides a sensitive and specific detection of S2-specific serum antibodies in experimentally and field-infected horses (22 of 24), without detectable reactivity with immune serum from uninfected (12 of 12) or vaccinated (29 of 29) horses. These data indicate that the S2-based diagnostic ELISA has the potential to accurately differentiate horses infected with EIAV from horses inoculated with an attenuated EIAV vaccine strain with a mutant S2 gene.

scholarly journals Suppression of Megakaryocyte Colony Growth by Plasma From Foals Infected With Equine Infectious Anemia Virus

Blood ◽  
1997 ◽  
Vol 90 (6) ◽  
pp. 2357-2363 ◽  
Author(s):  
Susan J. Tornquist ◽  
Timothy B. Crawford
Keyword(s):  
Neutralizing Antibodies ◽  
Equine Infectious Anemia Virus ◽  
Transforming Growth Factor ◽  
Bone Marrow Cells ◽  
Transforming Growth Factor Β ◽  
Colony Growth ◽  
Tnf Α ◽  
Equine Infectious Anemia ◽  
Anemia Virus

Abstract Foals infected with equine infectious anemia virus become thrombocytopenic 7 to 20 days after virus inoculation, and within a few days following the onset of detectable viremia. The thrombocytopenia is associated with suppression of platelet production. Possible mediators of suppression of thrombopoiesis include tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β), cytokines that are released during inflammation. To assess effects of plasma or serum from infected foals on megakaryocyte (MK) growth and maturation in vitro, equine low-density bone marrow cells were cultured for clonogenic and ploidy assays. Neutralizing antibodies to TNF-α and TGF-β were added to cultures to determine the contribution of these cytokines to suppression of thrombopoiesis. Plasma from the immediately pre-thrombocytopenia (Pre-Tp) period significantly reduced MK colony numbers. This suppression was partially reversed upon antibody neutralization of plasma TNF-α, TGF-β, or both. There were no differences in ploidy distribution of MK grown in the presence of preinfection serum compared with those grown in the presence of Pre-Tp serum. These results indicate that TNF-α and TGF-β may contribute to suppression of MK proliferation and represent likely factors in the pathogenesis of thrombocytopenia.

High Prevalence of Serum Antibodies to Equine Infectious Anemia Virus Reverse Transcriptase

1993 ◽  
Vol 9 (1) ◽  
pp. 7-11 ◽  
Author(s):  
ANTHONY L. DeVICO ◽  
CHARLES J. ISSEL ◽  
STUART F. J. Le GRICE ◽  
SUSAN L. PAYNE ◽  
RONALD C. MONTELARO ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Equine Infectious Anemia Virus ◽  
Serum Antibodies ◽  
High Prevalence ◽  
Equine Infectious Anemia ◽  
Anemia Virus

Suppression of Megakaryocyte Colony Growth by Plasma From Foals Infected With Equine Infectious Anemia Virus

Blood ◽  
1997 ◽  
Vol 90 (6) ◽  
pp. 2357-2363
Author(s):  
Susan J. Tornquist ◽  
Timothy B. Crawford
Keyword(s):  
Neutralizing Antibodies ◽  
Equine Infectious Anemia Virus ◽  
Transforming Growth Factor ◽  
Bone Marrow Cells ◽  
Transforming Growth Factor Β ◽  
Colony Growth ◽  
Tnf Α ◽  
Equine Infectious Anemia ◽  
Anemia Virus

Foals infected with equine infectious anemia virus become thrombocytopenic 7 to 20 days after virus inoculation, and within a few days following the onset of detectable viremia. The thrombocytopenia is associated with suppression of platelet production. Possible mediators of suppression of thrombopoiesis include tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β), cytokines that are released during inflammation. To assess effects of plasma or serum from infected foals on megakaryocyte (MK) growth and maturation in vitro, equine low-density bone marrow cells were cultured for clonogenic and ploidy assays. Neutralizing antibodies to TNF-α and TGF-β were added to cultures to determine the contribution of these cytokines to suppression of thrombopoiesis. Plasma from the immediately pre-thrombocytopenia (Pre-Tp) period significantly reduced MK colony numbers. This suppression was partially reversed upon antibody neutralization of plasma TNF-α, TGF-β, or both. There were no differences in ploidy distribution of MK grown in the presence of preinfection serum compared with those grown in the presence of Pre-Tp serum. These results indicate that TNF-α and TGF-β may contribute to suppression of MK proliferation and represent likely factors in the pathogenesis of thrombocytopenia.

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