Long terminal repeat sequences of equine infectious anaemia virus are a major determinant of cell tropism.

Payne, Susan; Celle, K La; Pei, Xiaofang; Xu, Qi; Shao, Hai; Steagall, Wendy K.; Perry, Stephanie T.; Fuller, Frederick J.

doi:10.1099/0022-1317-80-3-755

Cited by 28 publications

(37 citation statements)

References 12 publications

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“…De esta forma, se podría afirmar que de forma general no se puede asociar una distinta respuesta según el origen de las distintas cepas estudiadas, sugiriéndose la falta de relación con los distintos orígenes/tropismos de los virus. Sin embargo, se ha visto como los LTRs son de especial relevancia en determinar el tropismo celular en el virus de la anemia infecciosa equina (EIAV) y en el virus de la inmunodeficiencia felina (Payne et al, 1999). Además se ha demostrado como el tropismo celular de MVV está determinado por los LTR (Agnarsdóttir et al, 2000).…”

Section: Discussionunclassified

Efecto de la progesterona, cortisoly dhea sobre la actividad transcripcional del LRT del virus de Maedi-VIsna

Crespo¹,

Gómez-Lucı́a²,

Doménech³

2012

Revista Complutense De Ciencias Veterinarias

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RESUMENEstudios previos sugieren que, al igual que en otras infecciones por retrovirus, las hormonas esteroideas serían capaces de dirigir la expresión del virus de Maedi-Visna (MVV) mediante la interacción con los Elementos de Respuesta a Hormona (HRE) de la región promotora/reguladora LTR (Repeticiones Largas Terminales) del genoma del provirus. El objetivo de este trabajo fue la evaluación del efecto del cortisol, progesterona y dehidroepiandrosterona (DHEA) sobre la capacidad transcripcional de la región LTR de MVV mediante ensayos de transfección en fibroblastos ovinos con plásmidos pAcGFP (que contiene el gen para la GFP, proteína verde fluorescente) en los que se había clonado la región U3-cap del LTR de distintas cepas de MVV. La actividad transcripcional del LTR se evaluó a través de la cuantificación de la expresión de la GFP por citometría de flujo con las distintas concentraciones de cada hormona tras 48 horas de incubación. En la mayoría de los ensayos se observó un claro efecto inhibitorio de la transcripción del LTR a elevadas concentraciones hormonales, disminuyendo el efecto a medida que se diluía la hormona, llegando incluso en el caso de cortisol y de DHEA a producirse un incremento de la expresión a partir de 10 -7 M. En general no se pudo asociar una diferente respuesta con el origen de la cepa estudiada lo que sugiere que no

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Section: Discussionunclassified

Efecto de la progesterona, cortisoly dhea sobre la actividad transcripcional del LRT del virus de Maedi-VIsna

Crespo¹,

Gómez-Lucı́a²,

Doménech³

2012

Revista Complutense De Ciencias Veterinarias

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“…These observations have led us to propose that in tissue culture, alterations in the EIAV enhancer region may result from cell-specific utilization of different transcription factors (33). Consistent with this, longterm adaptation in tissue culture has been frequently associated with changes in the LTR enhancer (6,43). While adaptation of EIAV to new cell types in tissue culture, such as fibroblasts, has been a useful approach to facilitate the maintenance of virus stocks and study the molecular biology of the virus (20,21), fibroblast tropism of the virus is associated with loss of both in vivo virulence (41) and the ability of the adapted strain to replicate in macrophages (7).…”

mentioning

confidence: 83%

“…on May 11, 2018 by guest http://jvi.asm.org/ has been previously identified in some fibroblast-tropic EIAV isolates (43). Nucleotide changes that were fixed within the population resulted in introduction of a novel transcription factor binding site.…”

Section: Vol 79 2005 Effect Of Cell Tropism On the Eiav Ltr 5657mentioning

confidence: 94%

“…Sequence variation throughout the HIV long terminal repeat (LTR) between and within different clades of virus is documented; however, in general, nucleotide variation is limited within the HIV enhancer/promoter proximal region that usually consists of two NF-B and three Sp1 sites (52). In contrast to HIV, the LTR enhancer region of equine infectious anemia virus (EIAV) is one of the most variable regions of the EIAV genome in tissue culture isolates and different field isolates (6,25,36,43). A study that examined seven in vivo isolates demonstrated that 45% of the nucleotide positions within the LTR enhancer varied between the isolates whereas little to no variation was found in the rest of the LTR (36).…”

mentioning

confidence: 99%

“…EIAV LTR sequences influence the tropism of the virus (43). While EIAV expression in macrophages utilizes a repertoire of transcription factors to initiate transcription that includes the macrophage-specific factor PU.1, EIAV expression in fibroblasts is driven by a series of other, more generic transcription factors such as AML-1, Oct-1, and ATF-1 (32,34).…”

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confidence: 99%

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

Maury

Thompson

Jones

et al. 2005

J Virol

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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 EIAV wyo 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 EIAV wyo 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 EIAV wyo LTR was evolutionarily stable in vivo.

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Analysis of a non‐structural gene reveals evidence of possible hepatitis C virus (HCV) compartmentalization

Blackard

Welge

et al. 2011

Journal of Medical Virology

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Viral diversity is a hallmark of hepatitis C virus (HCV) infection; however, only limited data are available regarding HCV variability in extrahepatic sites, and none have systematically compared diversity in non-structural and structural genomic regions. Therefore, HCV diversity in the NS5B and envelope 1 (E1) hypervariable region 1 (HVR1) genes was evaluated in matched sera and peripheral blood mononuclear cells (PBMCs) obtained from 13 HCV-infected women. Multiple clonal sequences were compared to evaluate quasispecies diversity and viral compartmentalization in PBMCs. Genetic distances were higher for E1/HVR1 compared to NS5B in both the sera and PBMCs (p = 0.0511 and p = 0.0284). Genetic distances were higher in serum NS5B compared to PBMC NS5B (p = 0.0003); however, they were not different when comparing E1/HVR1 in sera to PBMCs. By phylogenetic analysis of NS5B, evidence of possible PBMC compartmentalization was observed for 1 woman, while statistical methods were consistent with PBMC compartmentalization for 6 women. Evidence of compartmentalization within a non-structural genomic region may suggest that viral adaptation to a unique extracellular microenvironment(s) may be required for efficient replication and could contribute to HCV persistence.

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Long terminal repeat sequences of equine infectious anaemia virus are a major determinant of cell tropism.

Cited by 28 publications

References 12 publications

Efecto de la progesterona, cortisoly dhea sobre la actividad transcripcional del LRT del virus de Maedi-VIsna

Efecto de la progesterona, cortisoly dhea sobre la actividad transcripcional del LRT del virus de Maedi-VIsna

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

Analysis of a non‐structural gene reveals evidence of possible hepatitis C virus (HCV) compartmentalization

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