Summary.
The Chinese equine infectious anemia virus (EIAV) donkey-leukocyte attenuated vaccine (DLV) provides a unique natural model system to study the attenuation mechanism and immunological control of lentivirus replication. Critical consensus mutations were identified between virulent Chinese EIAV strains and vaccine strains. Based on a full-length infectious clone of EIAV vaccine strain pLGFD3, two molecular clones, mFD5-4-7 and mFD7-2-11, were successfully constructed, in which 4 and 6 critical consensus mutations in the env gene of the vaccine strain were point-mutated to the wild-type sequence, respectively by an overlap PCR mutagenesis strategy. The infectivity, virulence, and pathogenesis of the constructed clones were investigated in vitro using a reverse transcriptase assay, an indirect immunofluorescence assay, observation of cytopathogenic effect, and virion observation as well as in vivo by inoculation of animals with the resulting infectious clones. The pathogenic symptoms in horses inoculated with mFD7-2-11 were more severe than those inoculated with mFD5-4-7, whereas no pathogenic symptoms were detected in animals inoculated with their parental clone pLGFD3 strain. The results indicate that the consensus mutation residues of the env region involved in this study play significant roles in the virulence and pathogenicity of EIAV. This will contribute to the elucidation of the attenuating and protective mechanisms of the Chinese EIAV vaccine.
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S Alexandersen S Carpenter (1991) ArticleTitleCharacterization of variable regions in the envelope and S3 open reading frame of equine infectious anemia virus J Virol 65 4255–4262 Occurrence Handle1649329 Occurrence Handle1:CAS:528:DyaK3MXlvF2rtr0%3D
TW Baba V Liska AH Khimani NB Ray PJ Dailey D Penninck R Bronson MF Greene HM McClure LN Martin RM Ruprecht (1999) ArticleTitleLive attenuated, multiply deleted simian immunodeficiency virus causes AIDS in infant and adult macaques Nat Med 5 194–203 Occurrence Handle9930868 Occurrence Handle1:CAS:528:DyaK1MXivVKrt7Y%3D Occurrence Handle10.1038/8859
JM Ball CL Swaggerty X Pei WS Lim X Xu VC Cox SL Payne (2005) ArticleTitleSU proteins from virulent and avirulent EIAV demonstrate distinct biological properties Virology 333 132–144 Occurrence Handle15708599 Occurrence Handle1:CAS:528:DC%2BD2MXhtleltrc%3D Occurrence Handle10.1016/j.virol.2004.12.022
M Cayabyab GB Karlsson BA Etemad-Moghadam W Hofmann T Steenbeke M Halloran JW Fanton MK Axthelm NL Letvin JG Sodroski (1999) ArticleTitleChanges in human immunodeficiency virus type 1 envelope glycoproteins responsible for the pathogenicity of a multiply passaged simian-human immunodeficiency virus (SHIV-HXBc2) J Virol 73 976–984 Occurrence Handle9882298 Occurrence Handle1:CAS:528:DyaK1MXmtlWkuw%3D%3D
B Chackerian LM Rudensey J Overbaugh (1997) ArticleTitleSpecific N-linked and O-linked glycosylation modifications in the envelope V1 domain of simian immunodeficiency virus variants that evolve in the host alter recognition by neutralizing antibodies J Virol 71 7719–7727 Occurrence Handle9311856 Occurrence Handle1:CAS:528:DyaK2sXmt1Omsb4%3D
LA Chakrabarti T Ivanovic C Cheng-Mayer (2002) ArticleTitleProperties of the surface envelope glycoprotein associated with virulence of simian-human immunodeficiency virus SHIV(SF33A) molecular clones J Virol 76 1588–1599 Occurrence Handle11799153 Occurrence Handle1:CAS:528:DC%2BD38XnvFyltw%3D%3D Occurrence Handle10.1128/JVI.76.4.1588-1599.2002
WP Cheevers TC McGuire (1985) ArticleTitleEquine infectious anemia virus: immunopathogenesis and persistence Rev Infect Dis 7 83–88 Occurrence Handle2984759 Occurrence Handle1:STN:280:BiqC28jms1M%3D
C Chen F Li RC Montelaro (2001) ArticleTitleFunctional roles of equine infectious anemia virus Gag p9 in viral budding and infection J Virol 75 9762–9770 Occurrence Handle11559809 Occurrence Handle1:CAS:528:DC%2BD3MXnt1GgsrY%3D Occurrence Handle10.1128/JVI.75.20.9762-9770.2001
YH Chong JM Ball CJ Issel RC Montelaro KE Rushlow (1991) ArticleTitleAnalysis of equine humoral immune responses to the transmembrane envelope glycoprotein (gp45) of equine infectious anemia virus J Virol 65 1013–1018 Occurrence Handle1846180 Occurrence Handle1:CAS:528:DyaK3MXnvFOmtg%3D%3D
JM Coffin (1995) ArticleTitleHIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy Science 267 483–489 Occurrence Handle7824947 Occurrence Handle1:CAS:528:DyaK2MXjsFShu7w%3D
L Coggins NL Norcross SR Nusbaum (1972) ArticleTitleDiagnosis of equine infectious anemia by immunodiffusion test Am J Vet Res 33 11–18 Occurrence Handle4333633 Occurrence Handle1:STN:280:CS2C3crjtFI%3D
RF Cook SL Berger KE Rushlow JM McManus SJ Cook S Harrold ML Raabe RC Montelaro CJ Issel (1995) ArticleTitleEnhanced sensitivity to neutralizing antibodies in a variant of equine infectious anemia virus is linked to amino acid substitutions in the surface unit envelope glycoprotein J Virol 69 1493–1499 Occurrence Handle7853482 Occurrence Handle1:CAS:528:DyaK2MXjslemt7k%3D
RF Cook C Leroux SJ Cook SL Berger DL Lichtenstein NN Ghabrial RC Montelaro CJ Issel (1998) ArticleTitleDevelopment and characterization of an in vivo pathogenic molecular clone of equine infectious anemia virus J Virol 72 1383–1393 Occurrence Handle9445039 Occurrence Handle1:CAS:528:DyaK1cXlt12rtw%3D%3D
RF Cook SJ Cook SL Berger C Leroux NN Ghabrial M Gantz PS Bolin MR Mousel RC Montelaro CJ Issel (2003) ArticleTitleEnhancement of equine infectious anemia virus virulence by identification and removal of suboptimal nucleotides Virology 313 588–603 Occurrence Handle12954224 Occurrence Handle1:CAS:528:DC%2BD3sXmvVOqsL0%3D Occurrence Handle10.1016/S0042-6822(03)00351-9
MD Daniel F Kirchhoff SC Czajak PK Sehgal RC Desrosiers (1992) ArticleTitleProtective effects of a live attenuated SIV vaccine with a deletion in the nef gene Science 258 1938–1941 Occurrence Handle1470917 Occurrence Handle1:CAS:528:DyaK3sXlslOitA%3D%3D
B Etemad-Moghadam Y Sun EK Nicholson M Fernandes K Liou R Gomila J Lee J Sodroski (2000) ArticleTitleEnvelope glycoprotein determinants of increased fusogenicity in a pathogenic simian-human immunodeficiency virus (SHIV-KB9) passaged in vivo J Virol 74 4433–4440 Occurrence Handle10756060 Occurrence Handle1:CAS:528:DC%2BD3cXislGqs7Y%3D Occurrence Handle10.1128/JVI.74.9.4433-4440.2000
B Etemad-Moghadam D Rhone T Steenbeke Y Sun J Manola R Gelman JW Fanton P Racz K Tenner-Racz MK Axthelm NL Letvin J Sodroski (2001) ArticleTitleMembrane-fusing capacity of the human immunodeficiency virus envelope proteins determines the efficiency of CD+ T-cell depletion in macaques infected by a simian-human immunodeficiency virus J Virol 75 5646–5655 Occurrence Handle11356972 Occurrence Handle1:CAS:528:DC%2BD3MXjvFyrsbc%3D Occurrence Handle10.1128/JVI.75.12.5646-5655.2001
WR Gallaher JM Ball RF Garry MC Griffin RC Montelaro (1989) ArticleTitleA general model for the transmembrane proteins of HIV and other retroviruses AIDS Res Hum Retrovir 5 431–440 Occurrence Handle2788443 Occurrence Handle1:CAS:528:DyaL1MXlslSkt7o%3D
RR Garrity G Rimmelzwaan A Minassian WP Tsai G Lin JJ de Jong J Goudsmit PL Nara (1997) ArticleTitleRefocusing neutralizing antibody response by targeted dampening of an immunodominant epitope J Immunol 159 279–289 Occurrence Handle9200464 Occurrence Handle1:CAS:528:DyaK2sXktFCnt74%3D
JS Gibbs DA Regier RC Desrosiers (1994) ArticleTitleConstruction and in vitro properties of SIVmac mutants with deletions in “nonessential” genes AIDS Res Hum Retrovir 10 607–616 Occurrence Handle7917522 Occurrence Handle1:CAS:528:DyaK2MXivFSisA%3D%3D Occurrence Handle10.1089/aid.1994.10.607
AA Glenn FJ Novembre (2004) ArticleTitleA single amino acid change in gp41 is linked to the macrophage-only replication phenotype of a molecular clone of simian immunodeficiency virus derived from the brain of a macaque with neuropathogenic infection Virology 325 297–307 Occurrence Handle15246269 Occurrence Handle1:CAS:528:DC%2BD2cXls1WksL8%3D Occurrence Handle10.1016/j.virol.2004.04.048
SA Hammond F Li BM McKeon SuffixSr SJ Cook CJ Issel RC Montelaro (2000) ArticleTitleImmune responses and viral replication in long-term inapparent carrier ponies inoculated with equine infectious anemia virus J Virol 74 5968–5981 Occurrence Handle10846078 Occurrence Handle1:CAS:528:DC%2BD3cXkt1eitbc%3D Occurrence Handle10.1128/JVI.74.13.5968-5981.2000
He X, Fan XJ, Jia B, Shen RX, Shao YM (2003) Study on the function of env gene in EIAV pathogenicity. In: The AIDS vaccine 2003. New York, E1-3
X He YM Shao F Xue XJ Fan RX Shen (2003) ArticleTitleConstruction of infectious chimeric clones of equine infectious anemia virus(EIAV) Chin J Virol 19 128–132 Occurrence Handle1:CAS:528:DC%2BD2cXitlGlu7g%3D
R Hofmann-Lehmann J Vlasak AL Williams AL Chenine HM McClure DC Anderson S O’Neil RM Ruprecht (2003) ArticleTitleLive attenuated, nef-deleted SIV is pathogenic in most adult macaques after prolonged observation Aids 17 157–166 Occurrence Handle12545074 Occurrence Handle1:CAS:528:DC%2BD3sXmsVSmuw%3D%3D Occurrence Handle10.1097/00002030-200301240-00004
L Howe C Leroux CJ Issel RC Montelaro (2002) ArticleTitleEquine 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 76 10588–10597 Occurrence Handle12368301 Occurrence Handle1:CAS:528:DC%2BD38XnvFGqurs%3D Occurrence Handle10.1128/JVI.76.21.10588-10597.2002
CJ Issel DW Horohov DF Lea WV Adams SuffixJr SD Hagius JM McManus AC Allison RC Montelaro (1992) ArticleTitleEfficacy of inactivated whole-virus and subunit vaccines in preventing infection and disease caused by equine infectious anemia virus J Virol 66 3398–3408 Occurrence Handle1316455 Occurrence Handle1:STN:280:DyaK383mtVKjuw%3D%3D
RP Johnson JD Lifson SC Czajak KS Cole KH Manson R Glickman J Yang DC Montefiori R Montelaro MS Wyand RC Desrosiers (1999) ArticleTitleHighly attenuated vaccine strains of simian immunodeficiency virus protect against vaginal challenge: inverse relationship of degree of protection with level of attenuation J Virol 73 4952–4961 Occurrence Handle10233957 Occurrence Handle1:CAS:528:DyaK1MXjtFerur8%3D
M Kinomoto M Yokoyama H Sato A Kojima T Kurata K Ikuta T Sata K Tokunaga (2005) ArticleTitleAmino acid 36 in the human immunodeficiency virus type 1 gp41 ectodomain controls fusogenic activity: implications for the molecular mechanism of viral escape from a fusion inhibitor J Virol 79 5996–6004 Occurrence Handle15857986 Occurrence Handle1:CAS:528:DC%2BD2MXkt1Wit7o%3D Occurrence Handle10.1128/JVI.79.10.5996-6004.2005
PD Kwong R Wyatt E Desjardins J Robinson JS Culp BD Hellmig RW Sweet J Sodroski WA Hendrickson (1999) ArticleTitleProbability analysis of variational crystallization and its application to gp120, the exterior envelope glycoprotein of type 1 human immunodeficiency virus (HIV-1) J Biol Chem 274 4115–4123 Occurrence Handle9933605 Occurrence Handle1:CAS:528:DyaK1MXhslahurc%3D Occurrence Handle10.1074/jbc.274.7.4115
C Leroux CJ Issel RC Montelaro (1997) ArticleTitleNovel and dynamic evolution of equine infectious anemia virus genomic quasispecies associated with sequential disease cycles in an experimentally infected pony J Virol 71 9627–9639 Occurrence Handle9371627 Occurrence Handle1:CAS:528:DyaK2sXnsVGjtrY%3D
C Leroux JK Craigo CJ Issel RC Montelaro (2001) ArticleTitleEquine infectious anemia virus genomic evolution in progressor and nonprogressor ponies J Virol 75 4570–4583 Occurrence Handle11312327 Occurrence Handle1:STN:280:DC%2BD3M3it1eisg%3D%3D Occurrence Handle10.1128/JVI.75.10.4570-4583.2001
F Li JK Craigo L Howe JD Steckbeck S Cook C Issel RC Montelaro (2003) ArticleTitleA live attenuated equine infectious anemia virus proviral vaccine with a modified S2 gene provides protection from detectable infection by intravenous virulent virus challenge of experimentally inoculated horses J Virol 77 7244–7253 Occurrence Handle12805423 Occurrence Handle1:CAS:528:DC%2BD3sXkvV2qtLc%3D Occurrence Handle10.1128/JVI.77.13.7244-7253.2003
H Liang XY Zhang T Shen X Tong Y Ma H Li WH Xiang RX Shen YM Shao (2005) ArticleTitleQuantification of equine infectious anemia virus RNA in experimental horse plasma by real-time RT-PCR assay Chin J Microbiol Immunol 25 IssueID12 1035–1039 Occurrence Handle1:CAS:528:DC%2BD2sXjvV2mtQ%3D%3D
DL Lichtenstein CJ Issel RC Montelaro (1996) ArticleTitleGenomic quasispecies associated with the initiation of infection and disease in ponies experimentally infected with equine infectious anemia virus J Virol 70 3346–3354 Occurrence Handle8648664 Occurrence Handle1:CAS:528:DyaK28XivF2nurg%3D
A Ly L Stamatatos (2000) ArticleTitleV2 loop glycosylation of the human immunodeficiency virus type 1 SF162 envelope facilitates interaction of this protein with CD4 and CCR5 receptors and protects the virus from neutralization by anti-V3 loop and anti-CD4 binding site antibodies J Virol 74 6769–6776 Occurrence Handle10888615 Occurrence Handle1:CAS:528:DC%2BD3cXkvFCmtrg%3D Occurrence Handle10.1128/JVI.74.15.6769-6776.2000
TC McGuire SR Leib RH Mealey DG Fraser DJ Prieur (2003) ArticleTitlePresentation and binding affinity of equine infectious anemia virus CTL envelope and matrix protein epitopes by an expressed equine classical MHC class I molecule J Immunol 171 1984–1993 Occurrence Handle12902502 Occurrence Handle1:CAS:528:DC%2BD3sXmtVWms7s%3D
RC Montelaro JM Ball KE Rushlow (1993) Equine retroviruses JA Levy (Eds) The retroviridae NumberInSeries2 Plenum Press New York/London 257–360
H Pang XG Kong H Sentsui Y Kono T Sugiura A Hasegawa H Akashi (1997) ArticleTitleGenetic variation of envelope gp90 gene of equine infectious anemia virus isolated from an experimentally infected horse J Vet Med Sci 59 1089–1095 Occurrence Handle9450237 Occurrence Handle1:CAS:528:DyaK1cXmt1WktA%3D%3D Occurrence Handle10.1292/jvms.59.1089
SL Payne FD Fang CP Liu BR Dhruva P Rwambo CJ Issel RC Montelaro (1987) ArticleTitleAntigenic variation and lentivirus persistence: variations in envelope gene sequences during EIAV infection resemble changes reported for sequential isolates of HIV Virology 161 321–331 Occurrence Handle2825406 Occurrence Handle1:CAS:528:DyaL1cXhvF2jtbk%3D Occurrence Handle10.1016/0042-6822(87)90124-3
SL Payne XF Pei B Jia A Fagerness FJ Fuller (2004) ArticleTitleInfluence of long terminal repeat and env on the virulence phenotype of equine infectious anemia virus J Virol 78 2478–2485 Occurrence Handle14963146 Occurrence Handle1:CAS:528:DC%2BD2cXhs1SltLs%3D Occurrence Handle10.1128/JVI.78.5.2478-2485.2004
CA Pikora (2004) ArticleTitleGlycosylation of the ENV spike of primate immunodeficiency viruses and antibody neutralization Curr HIV Res 2 243–254 Occurrence Handle15279588 Occurrence Handle1:CAS:528:DC%2BD2cXltlajtL4%3D Occurrence Handle10.2174/1570162043351264
MR Raabe CJ Issel RC Montelaro (1998) ArticleTitleEquine monocyte-derived macrophage cultures and their applications for infectivity and neutralization studies of equine infectious anemia virus J Virol Methods 71 87–104 Occurrence Handle9628225 Occurrence Handle1:CAS:528:DyaK1cXitVKgs70%3D Occurrence Handle10.1016/S0166-0934(97)00204-8
PM Rwambo CJ Issel WV Adams SuffixJr KA Hussain M Miller RC Montelaro (1990) ArticleTitleEquine infectious anemia virus (EIAV) humoral responses of recipient ponies and antigenic variation during persistent infection Arch Virol 111 199–212 Occurrence Handle2162160 Occurrence Handle1:STN:280:By%2BB1c3mt1A%3D Occurrence Handle10.1007/BF01311054
DC Sellon FJ Fuller TC McGuire (1994) ArticleTitleThe immunopathogenesis of equine infectious anemia virus Virus Res 32 111–138 Occurrence Handle8067050 Occurrence Handle1:STN:280:ByuA2cngsFQ%3D Occurrence Handle10.1016/0168-1702(94)90038-8
RX Shen ZD Xu XS He SX Zhang (1979) ArticleTitleStudy on immunological methods of equine infectious anemia Chin Agricult Sci 4 1–15
Shen RX, Wang ZM (1985) Development and use of an equine infectious aneamia donkey leukocyte attenuated vaccine. In: Equine Infectious Anemia: a national review of policies, programs, and future objectives. American Quarter Horse Association, Amarillo, Texas, pp 135–148
Shen RX, Wang ZY, Dong JP, Peng DC, Jia B, Lv XL, Zhao LP, Xiang WH (2001) Fetal donkey dermal cells adapted attenuated vaccine of equine infectious anemia virus and its culture method (Chinese patent No. 01123620), China
Z Si M Cayabyab J Sodroski (2001) ArticleTitleEnvelope glycoprotein determinants of neutralization resistance in a simian-human immunodeficiency virus (SHIV-HXBc2P 3.2) derived by passage in monkeys J Virol 75 4208–4218 Occurrence Handle11287570 Occurrence Handle1:CAS:528:DC%2BD3MXivFOkt7g%3D Occurrence Handle10.1128/JVI.75.9.4208-4218.2001
V Spyrou M Papanastassopoulou M Koumbati SV Nikolakaki G Koptopoulos (2005) ArticleTitleMolecular analysis of the proviral DNA of equine infectious anemia virus in mules in Greece Virus Res 107 63–72 Occurrence Handle15567035 Occurrence Handle1:CAS:528:DC%2BD2cXhtVantLbJ Occurrence Handle10.1016/j.virusres.2004.06.016
MS Wyand K Manson DC Montefiori JD Lifson RP Johnson RC Desrosiers (1999) ArticleTitleProtection by live, attenuated simian immunodeficiency virus against heterologous challenge J Virol 73 8356–8363 Occurrence Handle10482586 Occurrence Handle1:CAS:528:DyaK1MXlvFyrtLY%3D
YH Zheng T Nakaya H Sentsui M Kameoka M Kishi K Hagiwara H Takahashi Y Kono K Ikuta (1997) ArticleTitleInsertions, duplications and substitutions in restricted gp90 regions of equine infectious anaemia virus during febrile episodes in an experimentally infected horse J Gen Virol 78 IssueIDPt 4 807–820 Occurrence Handle9129653 Occurrence Handle1:CAS:528:DyaK2sXisVKqs78%3D
YH Zheng H Sentsui Y Kono K Ikuta (2000) ArticleTitleMutations occurring during serial passage of Japanese equine infectious anemia virus in primary horse macrophages Virus Res 68 93–98 Occurrence Handle10930666 Occurrence Handle1:CAS:528:DC%2BD3cXltlWhsrg%3D Occurrence Handle10.1016/S0168-1702(00)00147-7
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H. Liang and X. He contributed equally to this paper.
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Liang, H., He, X., Shen, R. et al. Combined amino acid mutations occurring in the envelope closely correlate with pathogenicity of EIAV. Arch Virol 151, 1387–1403 (2006). https://doi.org/10.1007/s00705-005-0718-3
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DOI: https://doi.org/10.1007/s00705-005-0718-3