Genomic quasispecies associated with the initiation of infection and disease in ponies experimentally infected with equine infectious anemia virus.
Abstract: Equine infectious anemia virus (EIAV) provides a uniquely dynamic system in which to study the mechanism and role of genomic variation in lentiviral persistence and pathogenesis. We have used a Shetland pony model of infection to investigate the association of specific long terminal repeat (LTR) and env gene genomic sequences with the initiation of infection and the onset of disease. We analyzed viral RNA isolated from a pathogenic stock of virus (EIAV PV) and from plasma taken during the first disease episode from two ponies infected with EIAV PV. Overall sequence variation within gp90 was low in EIAV PV and only slightly higher in plasma virus samples isolated from ponies during the first disease episode. However, a high proportion of mutations were localized to the principal neutralizing domain in EIAV PV and to the principal neutralizing domain and the gp90 hypervariable region in the two pony-derived samples. The rate of fixation of mutations was analyzed and determined to be approximately 4 x 10(-2) mutations per site per year. Sequence diversity within the U3 region of the LTR was extremely low, which suggested that the previously reported hypervariability of this region may be a consequence of selection for replication of EIAV in different host cells. The predominant EIAV PV env and LTR sequences were used to construct chimeric viruses so that the contribution of these sequences to viral pathogenicity could be examined. The chimeras replicated in cultured equine monocytes to the same extent as the parental nonpathogenic virus and did not cause disease in Shetland ponies by 120 days postinfection, suggesting that the EIAV genomic determinants of pathogenesis are complex.
Publication Date: 1996-06-01 PubMed ID: 8648664PubMed Central: PMC190205DOI: 10.1128/JVI.70.6.3346-3354.1996Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This research looks into the role of genomic variation in the Equine infectious anemia virus (EIAV) during infection and early disease stages in ponies. A variety of gene sequences were analyzed and subsequent constructed chimeric virus, created from these sequences, did not cause illness in test subjects.
Understanding the Role of Genomic Variation
- The Equine infectious anemia virus (EIAV) provides a useful system to study how genomic variation plays a part in persistence and pathogenesis of lentiviral diseases. These are slow-progressing diseases caused by lentiviruses, a family of retroviruses.
- Through a model of infection in Shetland ponies, the researchers looked into the connection of specific gene sequences with the start of infection and early disease stages. Two critical gene sequences, the long terminal repeat (LTR) and the env, were at the center of this investigation.
Analysis of Viral RNA Sequences
- An analysis was conducted on viral RNA, taken from a pathogenic EIAV stock and plasma samples from two ponies during the first disease episode after the infection.
- The researchers observed that the overall variation within one of the env genes, the gp90, was low in the EIAV stock and a bit higher in the plasma virus samples from the ponies.
- A significant number of mutations were seen in the principal neutralizing domain in the EIAV stock and in the same domain and gp90 hypervariable region in the pony samples.
- The rate of mutation fixation was determined to be about 4 x 10(-2) mutations per site per year.
Sequence Diversity and Chimeric Viruses
- The diversity level within the U3 region of the LTR was extremely low. It suggests that the previously mentioned hypervariable nature of this region might be due to selective replication of EIAV in various host cells.
- The most prevalent EIAV env and LTR sequences were used in creating chimeric viruses for observing their contribution to disease causation.
- The results showed that these chimeras replicated in cultivated equine monocytes to the same level as the parent nonpathogenic virus and did not result in disease in the ponies even by 120 days post-infection.
Conclusion
- The research suggests that EIAV’s genomic traits that determine pathogenesis are complicated. This complexity highlights the need for further research and understanding.
Cite This Article
APA
Lichtenstein DL, Issel CJ, Montelaro RC.
(1996).
Genomic quasispecies associated with the initiation of infection and disease in ponies experimentally infected with equine infectious anemia virus.
J Virol, 70(6), 3346-3354.
https://doi.org/10.1128/JVI.70.6.3346-3354.1996 Publication
Researcher Affiliations
- Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
MeSH Terms
- Amino Acid Sequence
- Animals
- Base Sequence
- Equine Infectious Anemia / virology
- Genome, Viral
- Horses
- Infectious Anemia Virus, Equine / genetics
- Molecular Sequence Data
- Repetitive Sequences, Nucleic Acid
- Viral Proteins / chemistry
Grant Funding
- 5R01CA49296 / NCI NIH HHS
References
This article includes 39 references
- Payne SL, Salinovich O, Nauman SM, Issel CJ, Montelaro RC. Course and extent of variation of equine infectious anemia virus during parallel persistent infections.. J Virol 1987 Apr;61(4):1266-70.
- Rushlow K, Olsen K, Stiegler G, Payne SL, Montelaro RC, Issel CJ. Lentivirus genomic organization: the complete nucleotide sequence of the env gene region of equine infectious anemia virus.. Virology 1986 Dec;155(2):309-21.
- Payne SL, Fang FD, Liu CP, Dhruva BR, Rwambo P, Issel CJ, Montelaro RC. Antigenic variation and lentivirus persistence: variations in envelope gene sequences during EIAV infection resemble changes reported for sequential isolates of HIV.. Virology 1987 Dec;161(2):321-31.
- Meyerhans A, Cheynier R, Albert J, Seth M, Kwok S, Sninsky J, Morfeldt-Månson L, Asjö B, Wain-Hobson S. Temporal fluctuations in HIV quasispecies in vivo are not reflected by sequential HIV isolations.. Cell 1989 Sep 8;58(5):901-10.
- Payne SL, Rushlow K, Dhruva BR, Issel CJ, Montelaro RC. Localization of conserved and variable antigenic domains of equine infectious anemia virus envelope glycoproteins using recombinant env-encoded protein fragments produced in Escherichia coli.. Virology 1989 Oct;172(2):609-15.
- Rwambo PM, Issel CJ, Adams WV Jr, Hussain KA, Miller M, Montelaro RC. Equine infectious anemia virus (EIAV) humoral responses of recipient ponies and antigenic variation during persistent infection.. Arch Virol 1990;111(3-4):199-212.
- Rwambo PM, Issel CJ, Hussain KA, Montelaro RC. In vitro isolation of a neutralization escape mutant of equine infectious anemia virus (EIAV).. Arch Virol 1990;111(3-4):275-80.
- Carpenter S, Alexandersen S, Long MJ, Perryman S, Chesebro B. Identification of a hypervariable region in the long terminal repeat of equine infectious anemia virus.. J Virol 1991 Mar;65(3):1605-10.
- Vartanian JP, Meyerhans A, Asjö B, Wain-Hobson S. Selection, recombination, and G----A hypermutation of human immunodeficiency virus type 1 genomes.. J Virol 1991 Apr;65(4):1779-88.
- Burns DP, Desrosiers RC. Selection of genetic variants of simian immunodeficiency virus in persistently infected rhesus monkeys.. J Virol 1991 Apr;65(4):1843-54.
- Alexandersen S, Carpenter S. Characterization of variable regions in the envelope and S3 open reading frame of equine infectious anemia virus.. J Virol 1991 Aug;65(8):4255-62.
- Baier M, Dittmar MT, Cichutek K, Kurth R. Development of vivo of genetic variability of simian immunodeficiency virus.. Proc Natl Acad Sci U S A 1991 Sep 15;88(18):8126-30.
- Johnson PR, Hamm TE, Goldstein S, Kitov S, Hirsch VM. The genetic fate of molecularly cloned simian immunodeficiency virus in experimentally infected macaques.. Virology 1991 Nov;185(1):217-28.
- Overbaugh J, Rudensey LM, Papenhausen MD, Benveniste RE, Morton WR. Variation in simian immunodeficiency virus env is confined to V1 and V4 during progression to simian AIDS.. J Virol 1991 Dec;65(12):7025-31.
- Ball JM, Rushlow KE, Issel CJ, Montelaro RC. Detailed mapping of the antigenicity of the surface unit glycoprotein of equine infectious anemia virus by using synthetic peptide strategies.. J Virol 1992 Feb;66(2):732-42.
- Perry ST, Flaherty MT, Kelley MJ, Clabough DL, Tronick SR, Coggins L, Whetter L, Lengel CR, Fuller F. The surface envelope protein gene region of equine infectious anemia virus is not an important determinant of tropism in vitro.. J Virol 1992 Jul;66(7):4085-97.
- Gao F, Yue L, White AT, Pappas PG, Barchue J, Hanson AP, Greene BM, Sharp PM, Shaw GM, Hahn BH. Human infection by genetically diverse SIVSM-related HIV-2 in west Africa.. Nature 1992 Aug 6;358(6386):495-9.
- McNearney T, Hornickova Z, Markham R, Birdwell A, Arens M, Saah A, Ratner L. Relationship of human immunodeficiency virus type 1 sequence heterogeneity to stage of disease.. Proc Natl Acad Sci U S A 1992 Nov 1;89(21):10247-51.
- Novembre FJ, Johnson PR, Lewis MG, Anderson DC, Klumpp S, McClure HM, Hirsch VM. Multiple viral determinants contribute to pathogenicity of the acutely lethal simian immunodeficiency virus SIVsmmPBj variant.. J Virol 1993 May;67(5):2466-74.
- Carvalho M, Derse D. The PU.1/Spi-1 proto-oncogene is a transcriptional regulator of a lentivirus promoter.. J Virol 1993 Jul;67(7):3885-90.
- Marthas ML, Ramos RA, Lohman BL, Van Rompay KK, Unger RE, Miller CJ, Banapour B, Pedersen NC, Luciw PA. Viral determinants of simian immunodeficiency virus (SIV) virulence in rhesus macaques assessed by using attenuated and pathogenic molecular clones of SIVmac.. J Virol 1993 Oct;67(10):6047-55.
- Payne SL, Rausch J, Rushlow K, Montelaro RC, Issel C, Flaherty M, Perry S, Sellon D, Fuller F. Characterization of infectious molecular clones of equine infectious anaemia virus.. J Gen Virol 1994 Feb;75 ( Pt 2):425-9.
- Koup RA, Safrit JT, Cao Y, Andrews CA, McLeod G, Borkowsky W, Farthing C, Ho DD. Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome.. J Virol 1994 Jul;68(7):4650-5.
- Couillin I, Culmann-Penciolelli B, Gomard E, Choppin J, Levy JP, Guillet JG, Saragosti S. Impaired cytotoxic T lymphocyte recognition due to genetic variations in the main immunogenic region of the human immunodeficiency virus 1 NEF protein.. J Exp Med 1994 Sep 1;180(3):1129-34.
- Maury W. Monocyte maturation controls expression of equine infectious anemia virus.. J Virol 1994 Oct;68(10):6270-9.
- Bosch ML, Andeweg AC, Schipper R, Kenter M. Insertion of N-linked glycosylation sites in the variable regions of the human immunodeficiency virus type 1 surface glycoprotein through AAT triplet reiteration.. J Virol 1994 Nov;68(11):7566-9.
- Wei X, Ghosh SK, Taylor ME, Johnson VA, Emini EA, Deutsch P, Lifson JD, Bonhoeffer S, Nowak MA, Hahn BH. Viral dynamics in human immunodeficiency virus type 1 infection.. Nature 1995 Jan 12;373(6510):117-22.
- Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, Markowitz M. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection.. Nature 1995 Jan 12;373(6510):123-6.
- Lichtenstein DL, Rushlow KE, Cook RF, Raabe ML, Swardson CJ, Kociba GJ, Issel CJ, Montelaro RC. Replication in vitro and in vivo of an equine infectious anemia virus mutant deficient in dUTPase activity.. J Virol 1995 May;69(5):2881-8.
- Wain-Hobson S, Sonigo P, Guyader M, Gazit A, Henry M. Erratic G-->A hypermutation within a complete caprine arthritis-encephalitis virus (CAEV) provirus.. Virology 1995 Jun 1;209(2):297-303.
- Kono Y, Kobayashi K, Fukunaga Y. Antigenic drift of equine infectious anemia virus in chronically infected horses.. Arch Gesamte Virusforsch 1973;41(1):1-10.
- Malmquist WA, Barnett D, Becvar CS. Production of equine infectious anemia antigen in a persistently infected cell line.. Arch Gesamte Virusforsch 1973;42(4):361-70.
- Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors.. Proc Natl Acad Sci U S A 1977 Dec;74(12):5463-7.
- Orrego A, Issel CJ, Montelaro RC, Adams WV Jr. Virulence and in vitro growth of a cell-adapted strain of equine infectious anemia virus after serial passage in ponies.. Am J Vet Res 1982 Sep;43(9):1556-60.
- Payne S, Parekh B, Montelaro RC, Issel CJ. Genomic alterations associated with persistent infections by equine infectious anaemia virus, a retrovirus.. J Gen Virol 1984 Aug;65 ( Pt 8):1395-9.
- Montelaro RC, Parekh B, Orrego A, Issel CJ. Antigenic variation during persistent infection by equine infectious anemia virus, a retrovirus.. J Biol Chem 1984 Aug 25;259(16):10539-44.
- Salinovich O, Payne SL, Montelaro RC, Hussain KA, Issel CJ, Schnorr KL. Rapid emergence of novel antigenic and genetic variants of equine infectious anemia virus during persistent infection.. J Virol 1986 Jan;57(1):71-80.
- Hahn BH, Shaw GM, Taylor ME, Redfield RR, Markham PD, Salahuddin SZ, Wong-Staal F, Gallo RC, Parks ES, Parks WP. Genetic variation in HTLV-III/LAV over time in patients with AIDS or at risk for AIDS.. Science 1986 Jun 20;232(4757):1548-53.
- Hussain KA, Issel CJ, Schnorr KL, Rwambo PM, Montelaro RC. Antigenic analysis of equine infectious anemia virus (EIAV) variants by using monoclonal antibodies: epitopes of glycoprotein gp90 of EIAV stimulate neutralizing antibodies.. J Virol 1987 Oct;61(10):2956-61.
Citations
This article has been cited 18 times.- Han X, Zhang P, Yu W, Xiang W, Li X. Amino acid mutations in the env gp90 protein that modify N-linked glycosylation of the Chinese EIAV vaccine strain enhance resistance to neutralizing antibodies.. Virus Genes 2016 Dec;52(6):814-822.
- Cervantes DT, Ball JM, Edwards J, Payne S. Horses naturally infected with EIAV harbor 2 distinct SU populations but are monophyletic with respect to IN.. Virus Genes 2016 Feb;52(1):71-80.
- Craigo JK, Ezzelarab C, Cook SJ, Liu C, Horohov D, Issel CJ, Montelaro RC. Protective efficacy of centralized and polyvalent envelope immunogens in an attenuated equine lentivirus vaccine.. PLoS Pathog 2015 Jan;11(1):e1004610.
- Craigo JK, Montelaro RC. Lessons in AIDS vaccine development learned from studies of equine infectious, anemia virus infection and immunity.. Viruses 2013 Dec 2;5(12):2963-76.
- Craigo JK, Ezzelarab C, Cook SJ, Chong L, Horohov D, Issel CJ, Montelaro RC. Envelope determinants of equine lentiviral vaccine protection.. PLoS One 2013;8(6):e66093.
- Wang X, Wang S, Lin Y, Jiang C, Ma J, Zhao L, Lv X, Wang F, Shen R, Zhou J. Unique evolution characteristics of the envelope protein of EIAV(LN₄₀), a virulent strain of equine infectious anemia virus.. Virus Genes 2011 Apr;42(2):220-8.
- Craigo JK, Barnes S, Cook SJ, Issel CJ, Montelaro RC. Divergence, not diversity of an attenuated equine lentivirus vaccine strain correlates with protection from disease.. Vaccine 2010 Nov 29;28(51):8095-104.
- Craigo JK, Barnes S, Zhang B, Cook SJ, Howe L, Issel CJ, Montelaro RC. An EIAV field isolate reveals much higher levels of subtype variability than currently reported for the equine lentivirus family.. Retrovirology 2009 Oct 20;6:95.
- Fidalgo-Carvalho I, Craigo JK, Barnes S, Costa-Ramos C, Montelaro RC. Characterization of an equine macrophage cell line: application to studies of EIAV infection.. Vet Microbiol 2009 Apr 14;136(1-2):8-19.
- Craigo JK, Zhang B, Barnes S, Tagmyer TL, Cook SJ, Issel CJ, Montelaro RC. Envelope variation as a primary determinant of lentiviral vaccine efficacy.. Proc Natl Acad Sci U S A 2007 Sep 18;104(38):15105-10.
- Craigo JK, Li F, Steckbeck JD, Durkin S, Howe L, Cook SJ, Issel C, Montelaro RC. Discerning an effective balance between equine infectious anemia virus attenuation and vaccine efficacy.. J Virol 2005 Mar;79(5):2666-77.
- Mealey RH, Leib SR, Pownder SL, McGuire TC. Adaptive immunity is the primary force driving selection of equine infectious anemia virus envelope SU variants during acute infection.. J Virol 2004 Sep;78(17):9295-305.
- Payne SL, Pei XF, Jia B, Fagerness A, Fuller FJ. Influence of long terminal repeat and env on the virulence phenotype of equine infectious anemia virus.. J Virol 2004 Mar;78(5):2478-85.
- Howe L, Leroux C, Issel CJ, Montelaro RC. Equine infectious anemia virus envelope evolution in vivo during persistent infection progressively increases resistance to in vitro serum antibody neutralization as a dominant phenotype.. J Virol 2002 Nov;76(21):10588-97.
- Leroux C, Craigo JK, Issel CJ, Montelaro RC. Equine infectious anemia virus genomic evolution in progressor and nonprogressor ponies.. J Virol 2001 May;75(10):4570-83.
- Cook RF, Leroux C, Cook SJ, Berger SL, Lichtenstein DL, Ghabrial NN, Montelaro RC, Issel CJ. Development and characterization of an in vivo pathogenic molecular clone of equine infectious anemia virus.. J Virol 1998 Feb;72(2):1383-93.
- Leroux C, Issel CJ, Montelaro RC. Novel and dynamic evolution of equine infectious anemia virus genomic quasispecies associated with sequential disease cycles in an experimentally infected pony.. J Virol 1997 Dec;71(12):9627-39.
- Zheng YH, Sentsui H, Nakaya T, Kono Y, Ikuta K. In vivo dynamics of equine infectious anemia viruses emerging during febrile episodes: insertions/duplications at the principal neutralizing domain.. J Virol 1997 Jul;71(7):5031-9.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists