Antigenic variation and lentivirus persistence: Variations in envelope gene sequences during EIAV infection resemble changes reported for sequential isolates of HIV

Payne, Susan; Fang, Fude; Liu, Chen-Pin; Dhruva, Bharati R.; Rwambo, P. M.; Issel, Charles J.; Montelaro, Ronald C.

doi:10.1016/0042-6822(87)90124-3

Cited by 109 publications

(109 citation statements)

References 30 publications

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“…Detailed serologic and genetic characterizations of the evolution of EIAV populations during chronic EIAV have demonstrated a close correlation between changes in viral neutralization specificity and variations in the sequence of the viral SU and TM proteins, respectively designated gp90 and gp45, that are observed in viral populations associated with sequential disease cycles (15,20,25,29,36). These studies of EIAV envelope variation have led to an identification of conserved and variable domains in the heavily glycosylated gp90 glycoprotein and have suggested that the presence of a hypervariable principal neutralizing domain (PND) in the V3 segment of the gp90 envelope glycoprotein (1,19,20).…”

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confidence: 99%

“…Extensive studies of EIAV recovered from experimentally infected equids during chronic disease have revealed a unique population of viral envelope quasispecies associated with each disease cycle, apparently reflecting the sequential evolution of antigenic variants that temporarily escape the prevailing host immune responses (20,21,25). Interestingly, a similar rate and extent of EIAV envelope evolution have been reported in progressor and nonprogressor ponies experimentally infected with a reference EIAV strain, suggesting ongoing viral variation and immune selection in the absence of clinical symptoms and relatively low levels of systemic virus replication (19).…”

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confidence: 99%

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Equine Infectious Anemia Virus Envelope Evolution In Vivo during Persistent Infection Progressively Increases Resistance to In Vitro Serum Antibody Neutralization as a Dominant Phenotype

Howe¹,

Leroux

Issel

et al. 2002

J Virol

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Equine infectious anemia virus (EIAV) infection of horses is characterized by well-defined waves of viremiaassociated with the sequential evolution of distinct viral populations displaying extensive envelope gp90 variation; however, a correlation of in vivo envelope evolution with in vitro serum neutralization phenotype remains undefined. Therefore, the goal of the present study was to utilize a previously defined panel of natural variant EIAV envelope isolates from sequential febrile episodes to characterize the effects of envelope variation during persistent infection on viral neutralization phenotypes and to define the determinants of EIAV envelope neutralization specificity. To assess the neutralization phenotypes of the sequential EIAV envelope variants, we determined the sensitivity of five variant envelopes to neutralization by a longitudinal panel of immune serum from the source infected pony. The results indicated that the evolution of the EIAV envelope sequences observed during sequential febrile episodes produced an increasingly neutralization-resistant phenotype. To further define the envelope determinants of EIAV neutralization specificity, we examined the neutralization properties of a panel of chimeric envelope constructs derived from reciprocal envelope domain exchanges between selected neutralization-sensitive and neutralization-resistant envelope variants. These results indicated that the EIAV gp90 V3 and V4 domains individually conferred serum neutralization resistance while other envelope segments in addition to V3 and V4 were evidently required for conferring total serum neutralization sensitivity. These data clearly demonstrate for the first time the influence of sequential gp90 variation during persistent infection in increasing envelope neutralization resistance, identify the gp90 V3 and V4 domains as the principal determinants of antibody neutralization resistance, and indicate distinct complex cooperative envelope domain interactions in defining sensitivity to serum antibody neutralization.

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confidence: 99%

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confidence: 99%

Equine Infectious Anemia Virus Envelope Evolution In Vivo during Persistent Infection Progressively Increases Resistance to In Vitro Serum Antibody Neutralization as a Dominant Phenotype

Howe¹,

Leroux

Issel

et al. 2002

J Virol

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“…EIAV antigenic and genomic variations have been previously examined at length (1,3,6,17,18,21,23,24,33,35,39,40,45,46). Studies of env gene variation demonstrate that infected animals maintain the virus as a quasispecies, as has been previously documented for other lentiviruses (17,18,23,24,26,34,35,45,46).…”

Section: Equine Infectious Anemia Virus (Eiav) Is a Macrophagetropic mentioning

confidence: 99%

Influence of Long Terminal Repeat and Env on the Virulence Phenotype of Equine Infectious Anemia Virus

Payne

Pei

Jia

et al. 2004

J Virol

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The molecular clones pSPeiav19 and p19/wenv17 of equine infectious anemia virus (EIAV) differ in env and long terminal repeats (LTRs) and produce viruses (EIAV 19 and EIAV 17 , respectively) of dramatically different virulence phenotypes. These constructs were used to generate a series of chimeric clones to test the individual contributions of LTR, surface (SU), and transmembrane (TM)/Rev regions to the disease potential of the highly virulent EIAV 17 . The LTRs of EIAV 19 and EIAV 17 differ by 16 nucleotides in the transcriptional enhancer region. The two viruses differ by 30 amino acids in SU, by 17 amino acids in TM, and by 8 amino acids in Rev. Results from in vivo infections with chimeric clones indicate that both LTR and env of EIAV 17 are required for the development of severe acute disease. In the context of the EIAV 17 LTR, SU appears to have a greater impact on virulence than does TM. EIAV 17SU , containing only the TM/Rev region from the avirulent parent, induced acute disease in two animals, while a similar infectious dose of EIAV 17TM (which derives SU from the avirulent parent) did not. Neither EIAV 17SU nor EIAV 17TM produced lethal disease when administered at infectious doses that were 6-to 30-fold higher than a lethal dose of the parental EIAV 17 . All chimeric clones replicated in primary equine monocyte-derived macrophages, and there was no apparent correlation between macrophage tropism and virulence phenotype.

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“…The significance of these observations is underscored by the relatedness of EIA virus (EIAV) and HIV. EIAV and HIV are genetically (Stephens et al, 1986;Rushlow et al, 1986) and antigenically similar, have at least one common cell target, the monocyte/macrophage (McGuire et al, 1971;Clabough-Sellon et al, 1992;Collman et al, 1990), and have a similar mechanism and pattern of antigenic variation in neutralization-sensitive epitopes present in their major viral envelope' glycoproteins (Payne et al, 1987;Clements et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

Corticosteroid Immunosuppression and Monoclonal Antibody-mediated CD5+ T Lymphocyte Depletion in Normal and Equine Infectious Anaemia Virus-carrier Horses

Tumas¹,

Hines

Perryman³

et al. 1994

Journal of General Virology

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The immune control of chronic equine infectious anaemia (EIA) lentiviral infection was investigated by specifically depleting CD5 + T lymphocytes in vivo with monoclonal antibody (MAb) or by immunosuppression with corticosteroids. MAb was given at 25 to 50 mg/day intravenously for 11 days. Murine IgG1 anti-equine CD2 MAb (n = 2 horses) or IgG1 (n = 2) and IgG2a control MAb (n = 2 normal; 2 EIA-infected) did not deplete CD2 + T lymphocytes in horses. Horses given murine IgG2a anti-CD5 MAb HB19A (n = 4 normal; 5 EIA-infected) had depletion of peripheral blood CD5 + T lymphocytes during treatment. These horses, however, maintained a residual population of CD2 ÷ T lymphocytes [15 (_+ 3) % of pretreatment numbers] that did not express CD5 but expressed either CD4 or CD8. These antigenically modulated CDS-T lymphocytes responded normally in vivo to intradermal inoculation with phytohaemagglutinin and in vitro to allogeneic leukocyte stimulation in one-way mixed lymphocyte reactions. EIA virus-infected horses (n = 5) did not develop recrudescent viraemia or disease following in vivo CD5 + T lymphocyte depletion. Immunosuppression of EIA virus-infected horses with corticosteroids (1 mg/kg body weight/day, intravenously for 9 days) resulted in detectable recrudescent EIA viraemia in 6/11 horses (55 %) and recrudescent disease in 9/11 horses (82 %). Normal horses (n = 3) treated with corticosteroids developed no clinical disease. These results demonstrate that the use of murine IgG2a MAbs to appropriate equine lymphocyte antigens will facilitate in vivo investigation of the role of T lymphocyte subpopulations in the control of EIA or other important equine diseases.

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Antigenic variation and lentivirus persistence: Variations in envelope gene sequences during EIAV infection resemble changes reported for sequential isolates of HIV

Cited by 109 publications

References 30 publications

Equine Infectious Anemia Virus Envelope Evolution In Vivo during Persistent Infection Progressively Increases Resistance to In Vitro Serum Antibody Neutralization as a Dominant Phenotype

Equine Infectious Anemia Virus Envelope Evolution In Vivo during Persistent Infection Progressively Increases Resistance to In Vitro Serum Antibody Neutralization as a Dominant Phenotype

Influence of Long Terminal Repeat and Env on the Virulence Phenotype of Equine Infectious Anemia Virus

Corticosteroid Immunosuppression and Monoclonal Antibody-mediated CD5+ T Lymphocyte Depletion in Normal and Equine Infectious Anaemia Virus-carrier Horses

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