An attenuated EIAV vaccine strain induces significantly different immune responses from its pathogenic parental strain although with similar in vivo replication pattern

State Key Laboratory of Veterinary Biotechnology, Division of Livestock Diseases, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, China.
Antiviral research (Impact Factor: 3.94). 08/2011; 92(2):292-304. DOI: 10.1016/j.antiviral.2011.08.016
Source: PubMed


The EIAV (equine infectious anemia virus) multi-species attenuated vaccine EIAV(DLV121) successfully prevented the spread of equine infectious anemia (EIA) in China in the 1970s and provided an excellent model for the study of protective immunity to lentiviruses. In this study, we compared immune responses induced by EIAV(DLV121) to immunity elicited by the virulent EIAV(LN40) strain and correlated immune responses to protection from infection. Horses were randomly grouped and inoculated with either EIAV(DLV121) (Vaccinees, Vac) or a sublethal dose of EIAV(LN40) (asymptomatic carriers, Car). Car horses became EIAV(LN40) carriers without disease symptoms. Two of the four Vac horses were protected against infection and the other two had delayed onset or reduced severity of EIA with a lethal EIAV(LN40) challenge 5.5 months post initial inoculation. In contrast, all three Car animals developed acute EIA and two succumbed to death. Specific humoral and cellular immune responses in both Vac and Car groups were evaluated for potential correlations with protection. These analyses revealed that although plasma viral loads remained between 10(3) and 10(5)copies/ml for both groups before EIAV(LN40) challenge, Vac-treated animals developed significantly higher levels of conformational dependent, Env-specific antibody, neutralizing antibody as well as significantly elevated CD4(+) T cell proliferation and IFN-γ-secreting CD8(+) T cells than those observed in EIAV(LN40) asymptomatic carriers. Further analysis of protected and unprotected cases in vaccinated horses identified that cellular response parameters and the reciprocal anti-p26-specific antibody titers closely correlated with protection against infection with the pathogenic EIAV(LN40). These data provide a better understanding of protective immunity to lentiviruses.

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    • "EIAVDLV34 (DLV34) is a cell culture-adapted EIAV pathogenic strain, which was derived by 33 passages of the virulent EIAVLN40 strain in donkey MDMs. Similar to EIAVLN40, inoculation with 104 TCID50 of DLV34 resulted in acute EIA in all the experimentally infected horses [19]. "
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    ABSTRACT: Equine lentivirus receptor 1 (ELR1) has been identified as the sole receptor for equine infectious anemia virus (EIAV) and is a member of the tumor necrosis factor receptor (TNFR) superfamily. In addition to the previously described membrane-associated form of ELR1, two other major alternative splicing variant mRNAs were identified in equine monocyte-derived macrophages (eMDMs). One major spliced species (ELR1-IN) contained an insertion of 153 nt, which resulted in a premature stop codon situated 561 nt upstream of the predicted membrane spanning domain. The other major species (ELR1-DE) has a deletion of 109 nt that causes a shift of the open reading frame and generates a stop codon 312 nt downstream. Because ELR1-DE presumably encodes a peptide of a mere 23 residues, only ELR1-IN was further analyzed. The expression of a soluble form of ELR1 (sELR1) by ELR1-IN was confirmed by Western blot and immunofluorescence analyses. Similar to ELR1, the transcription level of ELR1-IN varied among individual horses and at different time points in the same individuals. The ratio of ELR1-IN mRNA species to ELR1 mRNA was approximately 1∶2.5. Pre-incubation of the recombinant sELR1 with EIAV significantly inhibited EIAV infection in equine macrophages, the primary in vivo target cell of the virus. Fetal equine dermal (FED) cells are susceptible to EIAV in vitro, and the replication of EIAV in FED cells transiently transfected with ELR1-IN was markedly reduced when compared with replication in cells transfected with the empty vector. Finally, the expression levels of both forms of the EIAV receptor were significantly regulated by infection with this virus. Taken together, our data indicate that sELR1 acts as a secreted cellular factor that inhibits EIAV infection in host cells.
    Full-text · Article · Nov 2013 · PLoS ONE
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    • "These have demonstrated that compared to the highly virulent EIAV Liaoning parental strain (EIAV LN ), the attenuated phenotype of EIAV FDD13 is conferred by numerous genetic substitutions distributed throughout the viral genome (Jiang et al., 2010; Liang et al., 2006; Qi et al., 2010; Shen et al., 2006; Wei et al., 2009; Zhou et al., 2007). However, while this vaccine may have protected the Chinese equine population from disease, efficacy is not complete in experimental studies particularly with heterologous EIAV challenge viruses (Meng et al., 2011; Lin et al., 2011b; Zhang et al., 2007). An alternative approach has been to attenuate EIAV by the introduction of stop codons and/or a small deletion in the S2 open reading frame of the EIAV UK infectious molecular clone (EIAV UKDS2 ) (Cook et al., 1998; Li et al., 2003; Craigo et al., 2005, 2007a). "
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    ABSTRACT: A detailed description of equine infectious anemia virus and host responses to it are presented. Current control and eradication of the infection are discussed with suggestions for improvements to increase their effectiveness.
    Full-text · Article · Oct 2013 · Veterinary Microbiology
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    • "The plasma layer was ultracentrifuged at 100,000g for 1 h, and viral RNA in the precipitate was extracted using a QIAamp Viral RNA Mini Kit (Qiagen). The viral load in the plasma was analyzed using a previously described method (Jiang et al., 2011; Lin et al., 2011). The S2 nucleotide sequence of the infected viruses was examined at the 23, 65 and 200 dpi. "
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    ABSTRACT: The contribution of S2 accessory gene of equine infectious anemia virus (EIAV) to the virulence of pathogenic strains was investigated in the present study by reverse mutation of all four consensus S2 mutation sites in an attenuated EIAV proviral strain, FDDV3-8, to the corresponding sequences of a highly pathogenic strain DV117. The S2 reverse-mutated recombinant strain FDDVS2r1-2-3-4 replicated with similar kinetics to FDDV3-8 in cultivated target cells. In contrast to the results of other studies of EIAV with dysfunctional S2, reverse mutation of S2 only transiently and moderately increased the plasma viral load of inoculated horses, and induction of transient immunosuppression did not boost viral pathogenicity. In addition, inoculation of FDDVS2r1-2-3-4 induced partial protection to a challenge pathogenic virus. These results suggest that the attenuated EIAV vaccine strain with multiple mutations in multiple genes will not easily revert to a virulent phenotype.
    Full-text · Article · Jun 2013 · Virology
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