Journal of virology1997;
71(5);
3840-3852; doi: 10.1128/JVI.71.5.3840-3852.1997
Maturation of the cellular and humoral immune responses to persistent infection in horses by equine infectious anemia virus is a complex and lengthy process.
Abstract: Equine infectious anemia virus (EIAV) provides a natural model system by which immunological control of lentivirus infections may be studied. To date, no detailed study addressing in parallel both the humoral and cellular immune responses induced in horses upon infection by EIAV has been conducted. Therefore, we initiated the first comprehensive characterization of the cellular and humoral immune responses during clinical progression from chronic disease to inapparent stages of EIAV infection. Using new analyses of antibody avidity and antibody epitope conformation dependence that had not been previously employed in this system, we observed that the humoral immune response to EIAV required a 6- to 8-month period in which to fully mature. During this time frame, EIAV-specific antibody evolved gradually from a population characterized by low-avidity, nonneutralizing, and predominantly linear epitope specificity to an antibody population with an avidity of moderate to high levels, neutralizing activity, and predominantly conformational epitope specificity. Analyses of the cell-mediated immune response to EIAV revealed CD4+ and CD8+ major histocompatibility complex-restricted, EIAV-specific cytotoxic T-lymphocyte (CTL) activity apparent within 3 to 4 weeks postinfection, temporally correlating with the resolution of the primary viremia. After resolution of the initial viremia, EIAV-specific CTL activity differed greatly among the experimentally infected ponies, with some animals having readily detectable CTL activity while others had little measurable CTL activity. Thus, in contrast to the initial viremia, it appeared that no single immune parameter correlated with the resolution of further viremic episodes. Instead, immune control of EIAV infection during the clinically inapparent stage of infection appears to rely on a complex combination of immune system mechanisms to suppress viral replication that effectively functions only after the immune system has evolved to a fully mature state 6 to 8 months postinfection. These findings strongly imply the necessity for candidate EIAV and other lentivirus vaccines to achieve this immune system maturation for efficacious immunological control of lentivirus challenge.
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.
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.
The research focuses on understanding the immune response evoked by equine infectious anemia virus (EIAV) in horses. It observes that a mature immune response, encompassing both cellular and humoral components, takes as long as 6-8 months to fully develop following EIAV infection and is vital for effective control of the virus.
Characterization of Cellular and Humoral Immune Responses
The study is the first in-depth investigation into the progression of both cellular and humoral immune responses in horses infected with EIAV.
Utilizing advancements in antibody avidity and epitope conformation dependence analyses, the research identifies a marked change in the humoral immune response over 6-8 months post-infection.
The initial low-avidity, nonneutralizing antibodies specific to linear epitopes evolve into moderate to high-avidity, neutralizing antibodies mainly targeting conformational epitopes.
Temporal Correlation with Viremia Resolution
Cell-mediated immune responses, including Major Histocompatibility Complex (MHC)-restricted CD4+ and CD8+ cytotoxic T-lymphocyte (CTL) activities against EIAV, are detected as early as 3 to 4 weeks post-infection, alongside the resolution of primary viremia.
However, the level of EIAV-specific CTL activity varies widely among horses following the resolution of initial viremia, hinting at the lack of a singular immune parameter responsible for the control of subsequent viremia episodes.
Immune System Maturation and Viral Control
Control of EIAV infection during the clinically inapparent stage seems to rely on a comprehensive combination of immune mechanisms working to suppress viral replication.
This control only becomes effective once the immune system has fully matured, which takes 6 to 8 months post-infection, underlining the necessity for potential EIAV vaccines to encourage this immune maturation for effective control of lentivirus.
Cite This Article
APA
Hammond SA, Cook SJ, Lichtenstein DL, Issel CJ, Montelaro RC.
(1997).
Maturation of the cellular and humoral immune responses to persistent infection in horses by equine infectious anemia virus is a complex and lengthy process.
J Virol, 71(5), 3840-3852.
https://doi.org/10.1128/JVI.71.5.3840-3852.1997
Ball JM, Rao VS, Robey WG, Issel CJ, Montelaro RC. Lentivirus antigen purification and characterization: isolation of equine infectious anemia virus gag and env proteins in one step by reverse phase HPLC and application to human immunodeficiency virus glycoproteins.. J Virol Methods 1988 Mar-Apr;19(3-4):265-77.
Siliciano RF, Lawton T, Knall C, Karr RW, Berman P, Gregory T, Reinherz EL. Analysis of host-virus interactions in AIDS with anti-gp120 T cell clones: effect of HIV sequence variation and a mechanism for CD4+ cell depletion.. Cell 1988 Aug 12;54(4):561-75.
Lew AM, Anders RF, Edwards SJ, Langford CJ. Comparison of antibody avidity and titre elicited by peptide as a protein conjugate or as expressed in vaccinia.. Immunology 1988 Oct;65(2):311-4.
Cianciolo GJ, Bogerd H, Snyderman R. Human retrovirus-related synthetic peptides inhibit T lymphocyte proliferation.. Immunol Lett 1988 Sep;19(1):7-13.
Hedman K, Hietala J, Tiilikainen A, Hartikainen-Sorri AL, Räihä K, Suni J, Väänänen P, Pietiläinen M. Maturation of immunoglobulin G avidity after rubella vaccination studied by an enzyme linked immunosorbent assay (avidity-ELISA) and by haemolysis typing.. J Med Virol 1989 Apr;27(4):293-8.
Ruegg CL, Monell CR, Strand M. Inhibition of lymphoproliferation by a synthetic peptide with sequence identity to gp41 of human immunodeficiency virus type 1.. J Virol 1989 Aug;63(8):3257-60.
Leonard CK, Spellman MW, Riddle L, Harris RJ, Thomas JN, Gregory TJ. Assignment of intrachain disulfide bonds and characterization of potential glycosylation sites of the type 1 recombinant human immunodeficiency virus envelope glycoprotein (gp120) expressed in Chinese hamster ovary cells.. J Biol Chem 1990 Jun 25;265(18):10373-82.
Robinson JE, Holton D, Liu J, McMurdo H, Murciano A, Gohd R. A novel enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to HIV-1 envelope glycoproteins based on immobilization of viral glycoproteins in microtiter wells coated with concanavalin A.. J Immunol Methods 1990 Aug 28;132(1):63-71.
Parekh BS, Pau CP, Granade TC, Rayfield M, De Cock KM, Gayle H, Schochetman G, George JR. Oligomeric nature of transmembrane glycoproteins of HIV-2: procedures for their efficient dissociation and preparation of Western blots for diagnosis.. AIDS 1991 Aug;5(8):1009-13.
Yewdell JW, Bennink JR. Cell biology of antigen processing and presentation to major histocompatibility complex class I molecule-restricted T lymphocytes.. Adv Immunol 1992;52:1-123.
Hammond SA, Bollinger RC, Tobery TW, Silliciano RF. Transporter-independent processing of HIV-1 envelope protein for recognition by CD8+ T cells.. Nature 1993 Jul 8;364(6433):158-61.
Mascola JR, Mathieson BJ, Zack PM, Walker MC, Halstead SB, Burke DS. Summary report: workshop on the potential risks of antibody-dependent enhancement in human HIV vaccine trials.. AIDS Res Hum Retroviruses 1993 Dec;9(12):1175-84.
Selin LK, Nahill SR, Welsh RM. Cross-reactivities in memory cytotoxic T lymphocyte recognition of heterologous viruses.. J Exp Med 1994 Jun 1;179(6):1933-43.
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.
Moore JP, Cao Y, Ho DD, Koup RA. Development of the anti-gp120 antibody response during seroconversion to human immunodeficiency virus type 1.. J Virol 1994 Aug;68(8):5142-55.
Hammond SA, Johnson RP, Kalams SA, Walker BD, Takiguchi M, Safrit JT, Koup RA, Siliciano RF. An epitope-selective, transporter associated with antigen presentation (TAP)-1/2-independent pathway and a more general TAP-1/2-dependent antigen-processing pathway allow recognition of the HIV-1 envelope glycoprotein by CD8+ CTL.. J Immunol 1995 Jun 1;154(11):6140-56.
Siliciano RF, Soloski MJ. MHC class I-restricted processing of transmembrane proteins. Mechanism and biologic significance.. J Immunol 1995 Jul 1;155(1):2-5.
Gardner M, Rosenthal A, Jennings M, Yee J, Antipa L, Robinson E Jr. Passive immunization of rhesus macaques against SIV infection and disease.. AIDS Res Hum Retroviruses 1995 Jul;11(7):843-54.
Ferris RL, Buck C, Hammond SA, Woods AS, Cotter RJ, Takiguchi M, Igarashi Y, Ichikawa Y, Siliciano RF. Class I-restricted presentation of an HIV-1 gp41 epitope containing an N-linked glycosylation site. Implications for the mechanism of processing of viral envelope proteins.. J Immunol 1996 Jan 15;156(2):834-40.
CRESTFIELD AM, MOORE S, STEIN WH. The preparation and enzymatic hydrolysis of reduced and S-carboxymethylated proteins.. J Biol Chem 1963 Feb;238:622-7.
Siliciano RF, Keegan AD, Dintzis RZ, Dintzis HM, Shin HS. The interaction of nominal antigen with T cell antigen receptors. I. Specific binding of multivalent nominal antigen to cytolytic T cell clones.. J Immunol 1985 Aug;135(2):906-14.
Moharam I, Asala O, Reiche S, Hafez H, Beer M, Harder T, Grund C. Monoclonal antibodies specific for the hemagglutinin-neuraminidase protein define neutralizing epitopes specific for Newcastle disease virus genotype 2.VII from Egypt. Virol J 2021 Apr 26;18(1):86.
Wong KA, Harker JA, Dolgoter A, Marooki N, Zuniga EI. T Cell-Intrinsic IL-6R Signaling Is Required for Optimal ICOS Expression and Viral Control during Chronic Infection. J Immunol 2019 Sep 15;203(6):1509-1520.
Bonckaert C, van der Meulen K, Rodríguez-Ballarà I, Pedrazuela Sanz R, Martinez MF, Nauwynck HJ. Modified-live PRRSV subtype 1 vaccine UNISTRAIN(®) PRRS provides a partial clinical and virological protection upon challenge with East European subtype 3 PRRSV strain Lena. Porcine Health Manag 2016;2:12.
Harker JA, Wong KA, Dolgoter A, Zuniga EI. Cell-Intrinsic gp130 Signaling on CD4+ T Cells Shapes Long-Lasting Antiviral Immunity. J Immunol 2015 Aug 1;195(3):1071-81.
Harker JA, Dolgoter A, Zuniga EI. Cell-intrinsic IL-27 and gp130 cytokine receptor signaling regulates virus-specific CD4⁺ T cell responses and viral control during chronic infection. Immunity 2013 Sep 19;39(3):548-59.
Craigo JK, Ezzelarab C, Montelaro RC. Development of a high throughput, semi-automated, infectious center cell-based ELISA for equine infectious anemia virus. J Virol Methods 2012 Nov;185(2):221-7.
Harker JA, Lewis GM, Mack L, Zuniga EI. Late interleukin-6 escalates T follicular helper cell responses and controls a chronic viral infection. Science 2011 Nov 11;334(6057):825-9.
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.
Liu L, Wan Y, Wu L, Sun J, Li H, Li H, Ma L, Shao Y. Broader HIV-1 neutralizing antibody responses induced by envelope glycoprotein mutants based on the EIAV attenuated vaccine. Retrovirology 2010 Sep 1;7:71.
Mealey RH, Littke MH, Leib SR, Davis WC, McGuire TC. Cloning and large-scale expansion of epitope-specific equine cytotoxic T lymphocytes using an anti-equine CD3 monoclonal antibody and human recombinant IL-2. Vet Immunol Immunopathol 2007 Jul 15;118(1-2):121-8.
Steckbeck JD, Cole KS. Dissecting the humoral immune response to simian immunodeficiency virus: mechanisms of antibody-mediated virus neutralization. Immunol Res 2006;36(1-3):51-60.
Steckbeck JD, Grieser HJ, Sturgeon T, Taber R, Chow A, Bruno J, Murphy-Corb M, Montelaro RC, Cole KS. Dynamic evolution of antibody populations in a rhesus macaque infected with attenuated simian immunodeficiency virus identified by surface plasmon resonance. J Med Primatol 2006 Aug;35(4-5):248-60.
Mordasini F, Vogt HR, Zahno ML, Maeschli A, Nenci C, Zanoni R, Peterhans E, Bertoni G. Analysis of the antibody response to an immunodominant epitope of the envelope glycoprotein of a lentivirus and its diagnostic potential. J Clin Microbiol 2006 Mar;44(3):981-91.
Fraser DG, Mealey RH, McGuire TC. Selecting peptides to optimize Th1 responses to an equine lentivirus using HLA-DR binding motifs and defined HIV-1 Th peptides. Immunogenetics 2003 Oct;55(7):508-14.
Green TD, Montefiori DC, Ross TM. Enhancement of antibodies to the human immunodeficiency virus type 1 envelope by using the molecular adjuvant C3d. J Virol 2003 Feb;77(3):2046-55.
Ross TM, Xu Y, Green TD, Montefiori DC, Robinson HL. Enhanced avidity maturation of antibody to human immunodeficiency virus envelope: DNA vaccination with gp120-C3d fusion proteins. AIDS Res Hum Retroviruses 2001 Jun 10;17(9):829-35.
Mazzetti P, Giannecchini S, Del Mauro D, Matteucci D, Portincasa P, Merico A, Chezzi C, Bendinelli M. AIDS vaccination studies using an ex vivo feline immunodeficiency virus model: detailed analysis of the humoral immune response to a protective vaccine. J Virol 1999 Jan;73(1):1-10.
Richmond JF, Lu S, Santoro JC, Weng J, Hu SL, Montefiori DC, Robinson HL. Studies of the neutralizing activity and avidity of anti-human immunodeficiency virus type 1 Env antibody elicited by DNA priming and protein boosting. J Virol 1998 Nov;72(11):9092-100.
Cole KS, Murphey-Corb M, Narayan O, Joag SV, Shaw GM, Montelaro RC. Common themes of antibody maturation to simian immunodeficiency virus, simian-human immunodeficiency virus, and human immunodeficiency virus type 1 infections. J Virol 1998 Oct;72(10):7852-9.
Harmache A, Vitu C, Guiguen F, Russo P, Bertoni G, Pepin M, Vigne R, Suzan M. Priming with tat-deleted caprine arthritis encephalitis virus (CAEV) proviral DNA or live virus protects goats from challenge with pathogenic CAEV. J Virol 1998 Aug;72(8):6796-804.
Cole KS, Rowles JL, Jagerski BA, Murphey-Corb M, Unangst T, Clements JE, Robinson J, Wyand MS, Desrosiers RC, Montelaro RC. Evolution of envelope-specific antibody responses in monkeys experimentally infected or immunized with simian immunodeficiency virus and its association with the development of protective immunity. J Virol 1997 Jul;71(7):5069-79.