Identification of a hypervariable region in the long terminal repeat of equine infectious anemia virus.

1991 ◽  
Vol 65 (3) ◽  
pp. 1605-1610 ◽  
Author(s):  
S Carpenter ◽  
S Alexandersen ◽  
M J Long ◽  
S Perryman ◽  
B Chesebro
Keyword(s):  
Long Terminal Repeat ◽  
Equine Infectious Anemia Virus ◽  
Hypervariable Region ◽  
Terminal Repeat ◽  
Equine Infectious Anemia ◽  
Anemia Virus

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 Characterization of equine infectious anemia virus long terminal repeat.

1987 ◽  
Vol 61 (3) ◽  
pp. 743-747 ◽  
Author(s):  
D Derse ◽  
P L Dorn ◽  
L Levy ◽  
R M Stephens ◽  
N R Rice ◽  
...  
Keyword(s):  
Long Terminal Repeat ◽  
Equine Infectious Anemia Virus ◽  
Terminal Repeat ◽  
Equine Infectious Anemia ◽  
Anemia Virus

scholarly journals PU.1 Binding to ets Motifs within the Equine Infectious Anemia Virus Long Terminal Repeat (LTR) Enhancer: Regulation of LTR Activity and Virus Replication in Macrophages

2004 ◽  
Vol 78 (7) ◽  
pp. 3407-3418 ◽  
Author(s):  
Robert Hines ◽  
Brenda R. Sorensen ◽  
Madeline A. Shea ◽  
Wendy Maury
Keyword(s):  
Long Terminal Repeat ◽  
Binding Affinity ◽  
Equine Infectious Anemia Virus ◽  
Terminal Repeat ◽  
Binding Motif ◽  
Binding Studies ◽  
Proximal Site ◽  
Equine Infectious Anemia ◽  
Anemia Virus ◽  
The Impact

ABSTRACT Binding of the transcription factor PU.1 to its DNA binding motif regulates the expression of a number of B-cell- and myeloid-specific genes. The long terminal repeat (LTR) of macrophage-tropic strains of equine infectious anemia virus (EIAV) contains three PU.1 binding sites, namely an invariant promoter-proximal site as well as two upstream sites. We have previously shown that these sites are important for EIAV LTR activity in primary macrophages (W. Maury, J. Virol. 68:6270-6279, 1994). Since the sequences present in these three binding motifs are not identical, we sought to determine the role of these three sites in EIAV LTR activity. While DNase I footprinting studies indicated that all three sites within the enhancer were bound by recombinant PU.1, reporter gene assays demonstrated that the middle motif was most important for basal levels of LTR activity in macrophages and that the 5′ motif had little impact. The impact of the 3′ site became evident in Tat transactivation studies, in which the loss of the site reduced Tat-transactivated expression 40-fold. In contrast, elimination of the 5′ site had no effect on Tat-mediated activity. Binding studies were performed to determine whether differences in PU.1 binding affinity for the three sites correlated with the relative impact of each site on LTR transcription. While small differences were observed in the binding affinities of the three sites, with the promoter-proximal site having the strongest binding affinity, these differences could not account for the dramatic differences observed in the transcriptional effects. Instead, the promoter-proximal position of the 3′ motif appeared to be critical for its transcriptional impact and suggested that the PU.1 sites may serve different roles depending upon the location of the sites within the enhancer. Infectivity studies demonstrated that an LTR containing an enhancer composed of the three PU.1 sites was not sufficient to drive viral replication in macrophages. These findings indicate that while the promoter-proximal PU.1 site is the most critical site for EIAV LTR activity in the presence of Tat, other elements within the enhancer are needed for EIAV replication in macrophages.

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 Characterization of Equine Infectious Anemia Virus Long Terminal Repeat QuasispeciesIn VitroandIn Vivo

2018 ◽  
Vol 92 (8) ◽  
Author(s):  
Xue-Feng Wang ◽  
Qiang Liu ◽  
Yu-Hong Wang ◽  
Shuai Wang ◽  
Jie Chen ◽  
...  
Keyword(s):  
Long Terminal Repeat ◽  
Systematic Study ◽  
Equine Infectious Anemia Virus ◽  
Virulent Strain ◽  
Attenuated Virus ◽  
Equine Infectious Anemia ◽  
Anemia Virus ◽  
Over Time

ABSTRACTThe equine infectious anemia virus (EIAV) attenuated vaccine was developed by long-term passaging of a field-isolated virulent strain in cross-species hosts, followed by successive cultivation in cellsin vitro. To explore the molecular mechanism underlying the evolution of the EIAV attenuated vaccine, a systematic study focusing on long-terminal-repeat (LTR) variation in numerous virus strains ranging from virulent EIAV to attenuated EIAV was performed over time bothin vitroandin vivo. Two hypervariable regions were identified within the U3 region in the enhancer region (EHR) and the negative regulatory element (NRE) and within the R region in the transcription start site (TSS) and the Tat-activating region (TAR). Among these sites, variation in the U3 region resulted in the formation of additional transcription factor binding sites; this variation of thein vitro-adapted strains was consistent with the loss of pathogenicity. Notably, the same LTR variation pattern was observed bothin vitroandin vivo. Generally, the LTR variation in both the attenuated virus and the virulent strain fluctuated over timein vivo. Interestingly, the attenuated-virus-specific LTR variation was also detected in horses infected with the virulent strain, supporting the hypothesis that the evolution of an attenuated virus might have involved branching from EIAV quasispecies. This hypothesis was verified by phylogenetic analysis. The present systematic study examining the molecular evolution of attenuated EIAV from EIAV quasispecies may provide an informative model reflecting the evolution of similar lentiviruses.IMPORTANCEThe attenuated EIAV vaccine was the first lentiviral vaccine used to successfully control for equine infectious anemia in China. This vaccine provides an important reference for studying the relationship between EIAV gene variation and changes in biological characteristics. Importantly, the vaccine provides a model for the investigation of lentiviral quasispecies evolution. This study followed the “natural” development of the attenuated EIAV vaccine by use of a systematic analysis of LTR evolutionin vitroandin vivo. The results revealed that the increase in LTR variation with passaging was accompanied by a decrease in virulence, which indicated that LTR variability might parallel the attenuation of virulence. Interestingly, the attenuated-virus-specific LTR variation was also detected in virulent-strain-infected horses, a finding consistent with those of previous investigations ofgp90andS2evolution. Therefore, we present a hypothesis that the evolution of the attenuated virus may involve branching from EIAV quasispecies presentin vivo.

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