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.

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.

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.

In vitro Host Range of Equine Infectious Anemia Virus

Intervirology ◽  
1981 ◽  
Vol 16 (4) ◽  
pp. 225-232 ◽  
Author(s):  
Charles V. Benton ◽  
Bruce L. Brown ◽  
John S. Harshman ◽  
Raymond V. Gilden
Keyword(s):  
Host Range ◽  
Equine Infectious Anemia Virus ◽  
Equine Infectious Anemia ◽  
Anemia Virus

scholarly journals Effects of Long Terminal Repeat Sequence Variation on Equine Infectious Anemia Virus Replication in Vitro and in Vivo

Virology ◽  
1999 ◽  
Vol 263 (2) ◽  
pp. 408-417 ◽  
Author(s):  
Drew L. Lichtenstein ◽  
Jodi K. Craigo ◽  
Caroline Leroux ◽  
Keith E. Rushlow ◽  
R.Frank Cook ◽  
...  
Keyword(s):  
Long Terminal Repeat ◽  
Virus Replication ◽  
Sequence Variation ◽  
Equine Infectious Anemia Virus ◽  
Repeat Sequence ◽  
Equine Infectious Anemia ◽  
Anemia Virus ◽  
Terminal Repeat Sequence

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 Characterization of a Cytolytic Strain of Equine Infectious Anemia Virus

2003 ◽  
Vol 77 (4) ◽  
pp. 2385-2399 ◽  
Author(s):  
Wendy Maury ◽  
Patrick J. Wright ◽  
Sarahann Bradley
Keyword(s):  
In Vitro Selection ◽  
Equine Infectious Anemia Virus ◽  
Fibroblast Cell ◽  
Open Reading Frames ◽  
Fusogenic Activity ◽  
Equine Infectious Anemia ◽  
Anemia Virus ◽  
Receptor Interference

ABSTRACT A novel strain of equine infectious anemia virus (EIAV) called vMA-1c that rapidly and specifically killed infected equine fibroblasts (ED cells) but not other infectible cell lines was established. This strain was generated from an avirulent, noncytopathic strain of EIAV, MA-1. Studies with this new cytolytic strain of virus have permitted us to define viral parameters associated with EIAV-induced cell killing and begin to explore the mechanism. vMA-1c infection resulted in induction of rapid cell death, enhanced fusogenic activity, and increased rates of spread in equine fibroblasts compared to other strains of EIAV. The highly cytolytic nature of vMA-1c suggested that this strain might be superinfecting equine fibroblasts. Receptor interference studies demonstrated that prior infection of equine fibroblasts with EIAV did not alter the ability of vMA-1c to infect and kill these cells. In similar studies in a canine fibroblast cell line, receptor interference did occur. vMA-1c infection of equine fibroblasts was also associated with large quantities of unintegrated viral DNA, a well-established hallmark of retroviral superinfection. Cloning of the vMA-1c genome identified nucleotide changes that would result in at least one amino acid change in all viral proteins. A chimeric infectious molecular clone containing the vMA-1c tat, S2, and env open reading frames recapitulated most of the characteristics of vMA-1c, including superinfection, fibroblast killing, and fusogenic activity. In summary, in vitro selection for a strain of EIAV that rapidly killed cells resulted in the generation of a virus that was able to superinfect these cells, presumably by the use of a novel mechanism of cell entry. This phenotype mapped to the 3′ half of the genome.

scholarly journals Evolution of the Equine Infectious Anemia Virus Long Terminal Repeat during the Alteration of Cell Tropism

2005 ◽  
Vol 79 (9) ◽  
pp. 5653-5664 ◽  
Author(s):  
Wendy Maury ◽  
Robert J. Thompson ◽  
Quentin Jones ◽  
Sarahann Bradley ◽  
Tara Denke ◽  
...  
Keyword(s):  
Long Terminal Repeat ◽  
Equine Infectious Anemia Virus ◽  
Terminal Repeat ◽  
Binding Motif ◽  
Cell Tropism ◽  
Transcription Factor Binding Motif ◽  
Equine Infectious Anemia ◽  
Anemia Virus

ABSTRACT Equine infectious anemia virus (EIAV) is a lentivirus with in vivo cell tropism primarily for tissue macrophages; however, in vitro the virus can be adapted to fibroblasts and other cell types. Tropism adaptation is associated with both envelope and long terminal repeat (LTR) changes, and findings strongly suggest that these regions of the genome influence cell tropism and virulence. Furthermore, high levels of genetic variation have been well documented in both of these genomic regions. However, specific EIAV nucleotide or amino acid changes that are responsible for cell tropism changes have not been identified. A study was undertaken with the highly virulent, macrophage-tropic strain of virus EIAVwyo to identify LTR changes associated with alterations in cell tropism. We found the stepwise generation of a new transcription factor binding motif within the enhancer that was associated with adaptation of EIAV to endothelial cells and fibroblasts. An LTR that contained the new motif had enhanced transcriptional activity in fibroblasts, whereas the new site did not alter LTR activity in a macrophage cell line. This finding supports a previous prediction that selection for new LTR genetic variants may be a consequence of cell-specific selective pressures. Additional investigations of the EIAVwyo LTR were performed in vivo to determine if LTR evolution could be detected over the course of a 3-year infection. Consistent with previous in vivo findings, we observed no changes in the enhancer region of the LTR over that time period, indicating that the EIAVwyo LTR was evolutionarily stable in vivo.

scholarly journals A Live Attenuated Equine Infectious Anemia Virus Proviral Vaccine with a Modified S2 Gene Provides Protection from Detectable Infection by Intravenous Virulent Virus Challenge of Experimentally Inoculated Horses

2003 ◽  
Vol 77 (13) ◽  
pp. 7244-7253 ◽  
Author(s):  
Feng Li ◽  
Jodi K. Craigo ◽  
Laryssa Howe ◽  
Jonathan D. Steckbeck ◽  
Sheila Cook ◽  
...  
Keyword(s):  
Immune Responses ◽  
Equine Infectious Anemia Virus ◽  
High Dose ◽  
Accessory Gene ◽  
Virus Challenge ◽  
Equine Infectious Anemia ◽  
Anemia Virus ◽  
Vaccine Immunity

ABSTRACT Previous evaluations of inactivated whole-virus and envelope subunit vaccines to equine infectious anemia virus (EIAV) have revealed a broad spectrum of efficacy ranging from highly type-specific protection to severe enhancement of viral replication and disease in experimentally immunized equids. Among experimental animal lentivirus vaccines, immunizations with live attenuated viral strains have proven most effective, but the vaccine efficacy has been shown to be highly dependent on the nature and severity of the vaccine virus attenuation. We describe here for the first time the characterization of an experimental attenuated proviral vaccine, EIAVUKΔS2, based on inactivation of the S2 accessory gene to down regulate in vivo replication without affecting in vitro growth properties. The results of these studies demonstrated that immunization with EIAVUKΔS2 elicited mature virus-specific immune responses by 6 months and that this vaccine immunity provided protection from disease and detectable infection by intravenous challenge with a reference virulent biological clone, EIAVPV. This level of protection was observed in each of the six experimental horses challenged with the reference virulent EIAVPV by using a low-dose multiple-exposure protocol (three administrations of 10 median horse infectious doses [HID50], intravenous) designed to mimic field exposures and in all three experimentally immunized ponies challenged intravenously with a single inoculation of 3,000 HID50. In contrast, naïve equids subjected to the low- or high-dose challenge develop a detectable infection of challenge virus and acute disease within several weeks. Thus, these data demonstrate that the EIAV S2 gene provides an optimal site for modification to achieve the necessary balance between attenuation to suppress virulence and replication potential to sufficiently drive host immune responses to produce vaccine immunity to viral exposure.

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