In vivo evolution of the gp90 gene and consistently low plasma viral load during transient immune suppression demonstrate the safety of an attenuated equine infectious anemia virus (EIAV) vaccine

2009 ◽  
Vol 154 (5) ◽  
pp. 867-873 ◽  
Author(s):  
Jian Ma ◽  
Chenggang Jiang ◽  
Yuezhi Lin ◽  
Xuefeng Wang ◽  
Liping Zhao ◽  
...  
Keyword(s):  
Viral Load ◽  
Immune Suppression ◽  
Plasma Viral Load ◽  
Equine Infectious Anemia Virus ◽  
Equine Infectious Anemia ◽  
Anemia Virus

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 Subpopulations of Equine Infectious Anemia Virus Rev Coexist In Vivo and Differ in Phenotype

2003 ◽  
Vol 77 (22) ◽  
pp. 12122-12131 ◽  
Author(s):  
Prasith Baccam ◽  
Robert J. Thompson ◽  
Yuxing Li ◽  
Wendy O. Sparks ◽  
Michael Belshan ◽  
...  
Keyword(s):  
Complex Adaptive Systems ◽  
Nuclear Export ◽  
Adaptive Systems ◽  
Equine Infectious Anemia Virus ◽  
Environmental Changes ◽  
Regulatory Protein ◽  
Dependent Manner ◽  
Equine Infectious Anemia ◽  
Anemia Virus

ABSTRACT Lentiviruses exist in vivo as a population of related, nonidentical genotypes, commonly referred to as quasispecies. The quasispecies structure is characteristic of complex adaptive systems and contributes to the high rate of evolution in lentiviruses that confounds efforts to develop effective vaccines and antiviral therapies. Here, we describe analyses of genetic data from longitudinal studies of genetic variation in a lentivirus regulatory protein, Rev, over the course of disease in ponies experimentally infected with equine infectious anemia virus. As observed with other lentivirus data, the Rev variants exhibited a quasispecies character. Phylogenetic and partition analyses suggested that the Rev quasispecies comprised two distinct subpopulations that coexisted during infection. One subpopulation appeared to accumulate changes in a linear, time-dependent manner, while the other evolved radially from a common variant. Over time, the two subpopulations cycled in predominance coincident with changes in the disease state, suggesting that the two groups differed in selective advantage. Transient expression assays indicated the two populations differed significantly in Rev nuclear export activity. Chimeric proviral clones containing Rev genotypes representative of each population differed in rate and overall level of virus replication in vitro. The coexistence of genetically distinct viral subpopulations that differ in phenotype provides great adaptability to environmental changes within the infected host. A quasispecies model with multiple subpopulations may provide additional insight into the nature of lentivirus reservoirs and the evolution of antigenic and drug-resistant variants.

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 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.

scholarly journals A Particulate Viral Protein Vaccine Reduces Viral Load and Delays Progression to Disease in Immunized Ponies Challenged with Equine Infectious Anemia Virus

Virology ◽  
1999 ◽  
Vol 254 (1) ◽  
pp. 37-49 ◽  
Author(s):  
Scott A. Hammond ◽  
Sheila J. Cook ◽  
Louis D. Falo ◽  
Charles J. Issel ◽  
Ronald C. Montelaro
Keyword(s):  
Viral Load ◽  
Viral Protein ◽  
Equine Infectious Anemia Virus ◽  
Protein Vaccine ◽  
Equine Infectious Anemia ◽  
Anemia Virus

scholarly journals The S2 Gene of Equine Infectious Anemia Virus Is Dispensable for Viral Replication In Vitro

1998 ◽  
Vol 72 (10) ◽  
pp. 8344-8348 ◽  
Author(s):  
Feng Li ◽  
Bridget A. Puffer ◽  
Ronald C. Montelaro
Keyword(s):  
Equine Infectious Anemia Virus ◽  
Parental Virus ◽  
Target Cells ◽  
Monocyte Differentiation ◽  
Cell Culture Systems ◽  
Equine Infectious Anemia ◽  
Anemia Virus ◽  
First Time

ABSTRACT Equine infectious anemia virus (EIAV) contains the simplest genome among lentiviruses in that it encodes only three putative regulatory genes (S1, S2, S3) in addition to the canonical gag, pol, and envgenes, presumably reflecting its limited tropism to cells of monocyte/macrophage lineage. Tat and Rev functions have been assigned to S1 and S3, respectively, but the specific function for the S2 gene has yet to be determined. Thus, the function of S2 in virus replication in vitro was investigated by using an infectious molecular viral clone, EIAVUK. Various EIAVUK mutants lackingS2 were constructed, and their replication kinetics were examined in several equine cell culture systems, including the natural in vivo target equine macrophage cells. The EIAV S2 mutants showed replication kinetics similar to those of the parental virus in all of the tested primary and transformed equine cell cultures, without any detectable reversion of mutant genomes. The EIAVUKmutants also showed replication kinetics similar to those of the parental virus in an equine blood monocyte differentiation-maturation system. These results demonstrate for the first time that the EIAVS2 gene is not essential and does not appear to affect virus infection and replication properties in target cells in vitro.

scholarly journals Replication in vitro and in vivo of an equine infectious anemia virus mutant deficient in dUTPase activity.

1995 ◽  
Vol 69 (5) ◽  
pp. 2881-2888 ◽  
Author(s):  
D L Lichtenstein ◽  
K E Rushlow ◽  
R F Cook ◽  
M L Raabe ◽  
C J Swardson ◽  
...  
Keyword(s):  
Equine Infectious Anemia Virus ◽  
Equine Infectious Anemia ◽  
Virus Mutant ◽  
Anemia Virus

scholarly journals Naturally arising point mutations in non-essential domains of equine infectious anemia virus Rev alter Rev-dependent nuclear-export activity

2008 ◽  
Vol 89 (4) ◽  
pp. 1043-1048 ◽  
Author(s):  
Wendy O. Sparks ◽  
Karin S. Dorman ◽  
Sijun Liu ◽  
Susan Carpenter
Keyword(s):  
Genetic Variation ◽  
Nuclear Export ◽  
Equine Infectious Anemia Virus ◽  
Clinical Stage ◽  
Point Mutations ◽  
High Rate ◽  
Sample Population ◽  
Equine Infectious Anemia ◽  
Anemia Virus

Equine infectious anemia virus (EIAV) exhibits a high rate of genetic variation in vivo, and results in a clinically variable disease in infected horses. In vivo populations of EIAV have been characterized by the presence of distinct, genetic subpopulations of Rev that differ in phenotype and fluctuate in dominance in a manner coincident with each clinical stage of disease. This study examined the specific mutations that arose in vivo and altered the phenotype. The Rev protein was found to be highly conserved, and only 10 aa mutations were observed at a frequency greater than 10 % in the sample population. Nine of these mutations were capable of significantly altering Rev activity, either as single mutations in the context of the founder variant, or in the context of cumulatively fixed mutations. The results indicated that limited genetic variation outside the essential functional domains of Rev can alter the phenotype and may confer a selective advantage in vivo.

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