Decreased infectivity of a neutralization-resistant equine infectious anemia virus variant can be overcome by efficient cell-to-cell spread.
Abstract: Two variants of equine infectious anemia virus (EIAV) that differed in sensitivity to broadly neutralizing antibody were tested in direct competition assays. No differences were observed in the growth curves and relative fitness scores of EIAVs of principal neutralizing domain variants of groups 1 (EIAV(PND-1)) and 5 (EIAV(PND-5)), respectively; however, the neutralization-resistant EIAV(PND-5) variant was less infectious in single-round replication assays. Infectious center assays indicated similar rates of cell-to-cell spread, which was approximately 1,000-fold more efficient than cell-free infectivity. These data indicate that efficient cell-to-cell spread can overcome the decreased infectivity that may accompany immune escape and should be considered in studies assessing the relative levels of fitness among lentivirus variants, including HIV-1.
Publication Date: 2011-07-13 PubMed ID: 21752904PubMed Central: PMC3196457DOI: 10.1128/JVI.05349-11Google Scholar: Lookup
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- Journal Article
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- N.I.H.
- Extramural
Summary
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This study looks at two variations of the equine infectious anemia virus (EIAV) and how they react to a broad neutralizing antibody. While they found no differences in how the two variations grow and adapt, they did notice the more neutralization-resistant variant was less contagious in certain trials. However, this decrease in infectivity can be compensated by efficient cell-to-cell spread, which is a critical factor to consider when estimating the relative fitness levels among lentivirus variations, including HIV-1.
Understanding the EIAV Variants
The study involved two types of equine infectious anemia virus (EIAV), specifically varying in their sensitivity to a widely neutralizing antibody. These variants are:
- EIAV(PND-1): This is the first group, and its principal neutralizing domain (PND) is tagged as 1.
- EIAV(PND-5): This is the second group which is more resistant to neutralization, denoted by the principal neutralizing domain (PND) tag of 5.
Examination of EIAV Behavior
The researchers observed the growth curves and relative fitness scores of these EIAVs. They found that:
- There were no noticeable differences in growth and fitness between the two variations.
- The variant EIAV(PND-5) was less infectious in single-round replication assays. Despite its ability to resist neutralization, it was less capable of infecting in the given scenarios when compared to the EIAV(PND-1) variant.
The Role of Cell-to-Cell Spread
Another key aspect of the research was understanding the rates of cell-to-cell spread, a process that allows the virus to move directly from one cell to another:
- Infectious center assays were used to measure cell-to-cell viral spread, and both variants showed similar rates.
- The researchers noted that cell-to-cell spread was approximately 1,000 times more effective than cell-free infectivity. This means the virus is far more infectious when it moves directly from cell to cell instead of floating freely.
Implications for HIV-1 and Other Lentiviruses
The findings from this study are not only significant to understanding EIAV but also have broader implications for other viruses, like HIV-1, that belong to the same family, the lentivirus family. The study concludes by emphasizing that the role of efficient cell-to-cell spread in overcoming potentially decreased infectivity should be considered in efforts to assess the relative fitness among different lentivirus variants.
Cite This Article
APA
Wu W, Blythe DC, Loyd H, Mealey RH, Tallmadge RL, Dorman KS, Carpenter S.
(2011).
Decreased infectivity of a neutralization-resistant equine infectious anemia virus variant can be overcome by efficient cell-to-cell spread.
J Virol, 85(19), 10421-10424.
https://doi.org/10.1128/JVI.05349-11 Publication
Researcher Affiliations
- Department of Animal Science, Iowa State University, Ames, IA 50011, USA.
MeSH Terms
- Animals
- Antibodies, Neutralizing / immunology
- Antibodies, Viral / immunology
- Cell Line
- Infectious Anemia Virus, Equine / genetics
- Infectious Anemia Virus, Equine / growth & development
- Infectious Anemia Virus, Equine / immunology
- Infectious Anemia Virus, Equine / pathogenicity
- Mutation
- Neutralization Tests
- Virulence
Grant Funding
- K02 AI073101 / NIAID NIH HHS
- T32 AI007025 / NIAID NIH HHS
- R01 CA128568 / NCI NIH HHS
- AI073101 / NIAID NIH HHS
- CA128568 / NCI NIH HHS
References
This article includes 14 references
- 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.
- Bangham CRM. The immune control and cell-to-cell spread of human T-lymphotropic virus type 1.. J Gen Virol 2003 Dec;84(Pt 12):3177-3189.
- Carr JM, Hocking H, Li P, Burrell CJ. Rapid and efficient cell-to-cell transmission of human immunodeficiency virus infection from monocyte-derived macrophages to peripheral blood lymphocytes.. Virology 1999 Dec 20;265(2):319-29.
- Gupta P, Balachandran R, Ho M, Enrico A, Rinaldo C. Cell-to-cell transmission of human immunodeficiency virus type 1 in the presence of azidothymidine and neutralizing antibody.. J Virol 1989 May;63(5):2361-5.
- Hötzel I. Conservation of the human immunodeficiency virus type 1 gp120 V1/V2 stem/loop structure in the equine infectious anemia virus (EIAV) gp90.. AIDS Res Hum Retroviruses 2003 Oct;19(10):923-4.
- 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.
- Igakura T, Stinchcombe JC, Goon PK, Taylor GP, Weber JN, Griffiths GM, Tanaka Y, Osame M, Bangham CR. Spread of HTLV-I between lymphocytes by virus-induced polarization of the cytoskeleton.. Science 2003 Mar 14;299(5613):1713-6.
- Joos B, Trkola A, Fischer M, Kuster H, Rusert P, Leemann C, Böni J, Oxenius A, Price DA, Phillips RE, Wong JK, Hirschel B, Weber R, Günthard HF. Low human immunodeficiency virus envelope diversity correlates with low in vitro replication capacity and predicts spontaneous control of plasma viremia after treatment interruptions.. J Virol 2005 Jul;79(14):9026-37.
- Lobritz MA, Marozsan AJ, Troyer RM, Arts EJ. Natural variation in the V3 crown of human immunodeficiency virus type 1 affects replicative fitness and entry inhibitor sensitivity.. J Virol 2007 Aug;81(15):8258-69.
- Marozsan AJ, Moore DM, Lobritz MA, Fraundorf E, Abraha A, Reeves JD, Arts EJ. Differences in the fitness of two diverse wild-type human immunodeficiency virus type 1 isolates are related to the efficiency of cell binding and entry.. J Virol 2005 Jun;79(11):7121-34.
- Rangel HR, Weber J, Chakraborty B, Gutierrez A, Marotta ML, Mirza M, Kiser P, Martinez MA, Este JA, Quiñones-Mateu ME. Role of the human immunodeficiency virus type 1 envelope gene in viral fitness.. J Virol 2003 Aug;77(16):9069-73.
- Sponseller BA, Sparks WO, Wannemuehler Y, Li Y, Antons AK, Oaks JL, Carpenter S. Immune selection of equine infectious anemia virus env variants during the long-term inapparent stage of disease.. Virology 2007 Jun 20;363(1):156-65.
- Tallmadge RL, Brindley MA, Salmans J, Mealey RH, Maury W, Carpenter S. Development and characterization of an equine infectious anemia virus Env-pseudotyped reporter virus.. Clin Vaccine Immunol 2008 Jul;15(7):1138-40.
- Taylor SD, Leib SR, Carpenter S, Mealey RH. Selection of a rare neutralization-resistant variant following passive transfer of convalescent immune plasma in equine infectious anemia virus-challenged SCID horses.. J Virol 2010 Jul;84(13):6536-48.
Citations
This article has been cited 9 times.- Hull-Nye D, Meadows T, Smith SR, Schwartz EJ. Key Factors and Parameter Ranges for Immune Control of Equine Infectious Anemia Virus Infection.. Viruses 2023 Mar 6;15(3).
- Evans AB, Loyd H, Dunkelberger JR, van Tol S, Bolton MJ, Dorman KS, Dekkers JCM, Carpenter S. Antigenic and Biological Characterization of ORF2-6 Variants at Early Times Following PRRSV Infection.. Viruses 2017 May 16;9(5).
- Schwartz EJ, Smith RJ. Identifying the Conditions Under Which Antibodies Protect Against Infection by Equine Infectious Anemia Virus.. Vaccines (Basel) 2014 May 27;2(2):397-421.
- Schwartz EJ, Nanda S, Mealey RH. Antibody escape kinetics of equine infectious anemia virus infection of horses.. J Virol 2015 Jul;89(13):6945-51.
- Ma J, Wang SS, Lin YZ, Liu HF, Liu Q, Wei HM, Wang XF, Wang YH, Du C, Kong XG, Zhou JH, Wang X. Infection of equine monocyte-derived macrophages with an attenuated equine infectious anemia virus (EIAV) strain induces a strong resistance to the infection by a virulent EIAV strain.. Vet Res 2014 Aug 9;45(1):82.
- Castro EF, Campos RH, Cavallaro LV. Stability of the resistance to the thiosemicarbazone derived from 5,6-dimethoxy-1-indanone, a non-nucleoside polymerase inhibitor of bovine viral diarrhea virus.. PLoS One 2014;9(6):e100528.
- Wargo AR, Kurath G. Viral fitness: definitions, measurement, and current insights.. Curr Opin Virol 2012 Oct;2(5):538-45.
- Yakimovich A, Gumpert H, Burckhardt CJ, Lütschg VA, Jurgeit A, Sbalzarini IF, Greber UF. Cell-free transmission of human adenovirus by passive mass transfer in cell culture simulated in a computer model.. J Virol 2012 Sep;86(18):10123-37.
- Domingo E, Sheldon J, Perales C. Viral quasispecies evolution.. Microbiol Mol Biol Rev 2012 Jun;76(2):159-216.
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