The envelope protein （Env） of lentiviruses such as HIV, SIV, FIV and EIAV is larger than that of other retroviruses. The Chinese EIAV attenuated vaccine is based on Env and has helped to successfully control this vi...The envelope protein （Env） of lentiviruses such as HIV, SIV, FIV and EIAV is larger than that of other retroviruses. The Chinese EIAV attenuated vaccine is based on Env and has helped to successfully control this virus, demonstrating that envelope is crucial for vaccine. We compared Env variation of the four kinds of lentiviruses. Phylogenetic analysis showed that the evolutionary relationship of Env between HIV and SIV was the closest and they appeared to descend from a common ancestor, and the relationship of HIV and EIAV was the furthest. EIAV had the shortest Env length and the least number of potential N-linked glyeosylation sites （PNGS） as well as glyeosylation density compared to various immunodefieiency viruses. However, HIV had the longest Env length and the most PNGS. Moreover, the alignment of HIV and SIV showed that PNGS were primarily distributed within extraeellular membrane protein gp120 rather than transmembrane gp41. It implies that the size difference among these viruses is associated with a lentivirus specific function and also the diversity of env. There arc low levels of modification of glycosylation sites of Env and selection of optimal protective epitopes might be useful for development of an effective vaccine against HIV/AIDS.展开更多
The aim of this study was to determine the genomic evolutionary pattern of virulent equine infectious anemia virus （EIAV） during persistent infection. The evolutionary dynamics of proviral genomes were examined by c...The aim of this study was to determine the genomic evolutionary pattern of virulent equine infectious anemia virus （EIAV） during persistent infection. The evolutionary dynamics of proviral genomes were examined by challenging an EIAV seronegative equine （pony 1） and three EIAV vaccinated equines （ponies 4, 7, and 8） with the Chinese virulent strain EIAV- L. Ponies 1 and 7 succumbed to disease and were called progressors, while ponies 4 and 8 lacked clinical symptoms and were considered nonprogressors. Sequences spanning the V3, V4, and V5 hyper-variable regions of the EIAV-L envelope gp90 gene were sequenced from each pony as evolutionary markers of the provirus. The proviral genome of the EIAV-L inoculum evolved during persistent infection and displayed different patterns between EIA progressors and nonprogressors. Inoculum-like variants were isolated from nonprogressors during persistent infection, but only from progressors during acute infection. Variant mutations from nonprogressors were dispersed throughout the sequenced region, while those from progressors were predominantly localized to V3. Humoral immunity and virus variant population selection analyses indicated that immune selection was positive in chronically infected progressors and weak in nonprogressors. In-frame stop codons were frequently localized to a defect ＂hot spot＂. The high number of defective variants in nonprogressors may promote disease survival.展开更多
Equine infectious anemia virus strain L (EIAV-L) is the parental virulent virus of equine infectious anemia donkey leukocyte attenuated vaccine (DLA EIAV). In this study, peripheral blood leukocytes(PBL) were collecte...Equine infectious anemia virus strain L (EIAV-L) is the parental virulent virus of equine infectious anemia donkey leukocyte attenuated vaccine (DLA EIAV). In this study, peripheral blood leukocytes(PBL) were collected from a horse infected with EIAV-L.The PBL DNAs were extracted.The EIAV-L proviral DNA was amplified in four parts covering the entire proviral genomic sequence by polymerase chain reaction (PCR). Each of the four parts was cloned into the plasmid pBluescript SK, and the recombinant plasmids were designated as p2.8, p2.4. p3.1, and p1.2 respectively. After identification with restriction digestion, the inserts within the four plasmids were sequenced. The complete nucleotide sequence of EIAV-L provirus was determined by analyzing each of the four parts and connecting them as a whole. The genome of EIAV-L is 8235 bp in length, and G + C content is 38%. The comparison analysis by the computer software DNASIS showed that the sequence of EIAV-L shares 98.4% and 96.9% identities with that of D-A EIAV and DLA EIAV respectively. The high homology between these strains showed that they were genetically related. The homology between EIAV-L and D-A EIAV is higher than that between EIAV-L and DLA EIAV, and this is consistent with the derivation progress of DLA EIAV. At both ends of EIAV-L provirus, there is an identical long terminal repeat (LTR) sequence of 316bp in length. The LTR consists of U3, R, and U5 regions. The genome of EIAV-L provirus has three long open reading frames(ORF) corresponding to gag, pol and env genes respectively. The gag gene is 1200bp and located at position 613-1912nt. The pol gene is 3402bp and located at position 1708-5109nt. There is a termination codon within the env dividing it into two parts, envl of 699bp (position 5305-6003nt)and env2 of 1827bp (position 6073-7899nt). The provirus has three additional small ORFs: S1, S2 and S3 with sizes of 153bp(position 5113-5265nt), 204bp(position 5279-5482nt)and 402bp(position 7245-7646nt) respectively.展开更多
Equine Infectious Anemia Virus (EIAV) is a retrovirus that establishes a persistent infection in horses and ponies. The virus is in the same lentivirus subgroup that includes human immunodeficiency virus (HIV). The si...Equine Infectious Anemia Virus (EIAV) is a retrovirus that establishes a persistent infection in horses and ponies. The virus is in the same lentivirus subgroup that includes human immunodeficiency virus (HIV). The similarities between these two viruses make the study of the immune response to EIAV relevant to research on HIV. We developed a mathematical model of within-host EIAV infection dynamics that contains both humoral and cell-mediated immune responses. Analysis of the model yields results on thresholds that would be necessary for a combined immune response to successfully control infection. Numerical simulations are presented to illustrate the results. These findings have the potential to lead to immunological control measures for lentiviral infection.展开更多
Equine infectious anemia virus(EIAV)is a member of the lentivirus genus in the Retroviridae family and is considered an animal model for HIV/AIDS research.An attenuated EIAV vaccine,which was successfully developed in...Equine infectious anemia virus(EIAV)is a member of the lentivirus genus in the Retroviridae family and is considered an animal model for HIV/AIDS research.An attenuated EIAV vaccine,which was successfully developed in the 1970s by classical serial passage techniques,is the first and only lentivirus vaccine that has been widely used to date.Restriction factors are cellular proteins that provide an early line of defense against viral replication and spread by interfering with various critical steps in the viral replication cycle.However,viruses have evolved specific mechanisms to overcome these host barriers through adaptation.The battle between the viruses and restriction factors is actually a natural part of the viral replication process,which has been well studied in human immunodeficiency virus type 1(HIV-1).EIAV has the simplest genome composition of all lentiviruses,making it an intriguing subject for understanding how the virus employs its limited viral proteins to overcome restriction factors.In this review,we summarize the current literature on the interactions between equine restriction factors and EIAV.The features of equine restriction factors and the mechanisms by which the EIAV counteract the restriction suggest that lentiviruses employ diverse strategies to counteract innate immune restrictions.In addition,we present our insights on whether restriction factors induce alterations in the phenotype of the attenuated EIAV vaccine.展开更多
Proviral DNA was extracted from donkey leukocyte infected with Chinese donkey leukocyte attenuated equine infectious anemia virus(DLA-EIAV), and peripheral blood lymphocytes(PBL) from a horse infected with the virulen...Proviral DNA was extracted from donkey leukocyte infected with Chinese donkey leukocyte attenuated equine infectious anemia virus(DLA-EIAV), and peripheral blood lymphocytes(PBL) from a horse infected with the virulent EIAV strain Liaoning(EIAV L). The entire proviral DNA from both viruses was cloned and sequenced. The lengths of complete genomic sequences of DLA-EIAV and EIAV L provirus were 8266 bp and 8235 bp, respectively. Sequence comparison indicated that DLA-EIAV shares 97.0% and 97.5% in sequence homology with EIAV L and donkey-adapted EIAV(DA-EIAV), respectively. Lots of variations occurred in long terminal repeat(LTR, consisting of U3, R, U5), ORF S2, and env regions between DLA-EIAV and EIAV L. The nucleotide sequence differences of the two viruses in U3, R, U5, ORF S2, and env are 13.2%, 7.5%, 5.1%, 3.9%, and 2.7%, respectively, and predicted amino acid sequence differences in env and S2 coding regions are 4.4% and 8.8%, respectively. Six conserved regions are characterized in Gp90. There is a cis-activating GATA motif in ENH of DLA-EIAV and EIAV L. Two N-linked glycosylation sites disappeared in DLA-EIAV Gp90 in comparison with that of EIAV L. A bHLH transcription factor binding consensus sequence was found in LTR of DLA-EIAV but not in EIAV L. Furthermore, there is a mutation in the stem of DLA-EIAV TAR resulting in formation of a uridine tuber. Further study is needed to uncover the relationship between sequence changes and their biological functions of DLA-EIAV and L.展开更多
基金Natural Science Foundation of China(30970162)Tianjin Municipal Science and Technology Foundation(08ZCGHHZ01800)
文摘The envelope protein （Env） of lentiviruses such as HIV, SIV, FIV and EIAV is larger than that of other retroviruses. The Chinese EIAV attenuated vaccine is based on Env and has helped to successfully control this virus, demonstrating that envelope is crucial for vaccine. We compared Env variation of the four kinds of lentiviruses. Phylogenetic analysis showed that the evolutionary relationship of Env between HIV and SIV was the closest and they appeared to descend from a common ancestor, and the relationship of HIV and EIAV was the furthest. EIAV had the shortest Env length and the least number of potential N-linked glyeosylation sites （PNGS） as well as glyeosylation density compared to various immunodefieiency viruses. However, HIV had the longest Env length and the most PNGS. Moreover, the alignment of HIV and SIV showed that PNGS were primarily distributed within extraeellular membrane protein gp120 rather than transmembrane gp41. It implies that the size difference among these viruses is associated with a lentivirus specific function and also the diversity of env. There arc low levels of modification of glycosylation sites of Env and selection of optimal protective epitopes might be useful for development of an effective vaccine against HIV/AIDS.
基金supported by grants from the National High Technology R&D Program of China (863 Program,2001AA223041)the National Natural Science Foundation of China (30170706)
文摘The aim of this study was to determine the genomic evolutionary pattern of virulent equine infectious anemia virus （EIAV） during persistent infection. The evolutionary dynamics of proviral genomes were examined by challenging an EIAV seronegative equine （pony 1） and three EIAV vaccinated equines （ponies 4, 7, and 8） with the Chinese virulent strain EIAV- L. Ponies 1 and 7 succumbed to disease and were called progressors, while ponies 4 and 8 lacked clinical symptoms and were considered nonprogressors. Sequences spanning the V3, V4, and V5 hyper-variable regions of the EIAV-L envelope gp90 gene were sequenced from each pony as evolutionary markers of the provirus. The proviral genome of the EIAV-L inoculum evolved during persistent infection and displayed different patterns between EIA progressors and nonprogressors. Inoculum-like variants were isolated from nonprogressors during persistent infection, but only from progressors during acute infection. Variant mutations from nonprogressors were dispersed throughout the sequenced region, while those from progressors were predominantly localized to V3. Humoral immunity and virus variant population selection analyses indicated that immune selection was positive in chronically infected progressors and weak in nonprogressors. In-frame stop codons were frequently localized to a defect ＂hot spot＂. The high number of defective variants in nonprogressors may promote disease survival.
基金by National Science Foundation of China(No.39470535).
文摘Equine infectious anemia virus strain L (EIAV-L) is the parental virulent virus of equine infectious anemia donkey leukocyte attenuated vaccine (DLA EIAV). In this study, peripheral blood leukocytes(PBL) were collected from a horse infected with EIAV-L.The PBL DNAs were extracted.The EIAV-L proviral DNA was amplified in four parts covering the entire proviral genomic sequence by polymerase chain reaction (PCR). Each of the four parts was cloned into the plasmid pBluescript SK, and the recombinant plasmids were designated as p2.8, p2.4. p3.1, and p1.2 respectively. After identification with restriction digestion, the inserts within the four plasmids were sequenced. The complete nucleotide sequence of EIAV-L provirus was determined by analyzing each of the four parts and connecting them as a whole. The genome of EIAV-L is 8235 bp in length, and G + C content is 38%. The comparison analysis by the computer software DNASIS showed that the sequence of EIAV-L shares 98.4% and 96.9% identities with that of D-A EIAV and DLA EIAV respectively. The high homology between these strains showed that they were genetically related. The homology between EIAV-L and D-A EIAV is higher than that between EIAV-L and DLA EIAV, and this is consistent with the derivation progress of DLA EIAV. At both ends of EIAV-L provirus, there is an identical long terminal repeat (LTR) sequence of 316bp in length. The LTR consists of U3, R, and U5 regions. The genome of EIAV-L provirus has three long open reading frames(ORF) corresponding to gag, pol and env genes respectively. The gag gene is 1200bp and located at position 613-1912nt. The pol gene is 3402bp and located at position 1708-5109nt. There is a termination codon within the env dividing it into two parts, envl of 699bp (position 5305-6003nt)and env2 of 1827bp (position 6073-7899nt). The provirus has three additional small ORFs: S1, S2 and S3 with sizes of 153bp(position 5113-5265nt), 204bp(position 5279-5482nt)and 402bp(position 7245-7646nt) respectively.
文摘Equine Infectious Anemia Virus (EIAV) is a retrovirus that establishes a persistent infection in horses and ponies. The virus is in the same lentivirus subgroup that includes human immunodeficiency virus (HIV). The similarities between these two viruses make the study of the immune response to EIAV relevant to research on HIV. We developed a mathematical model of within-host EIAV infection dynamics that contains both humoral and cell-mediated immune responses. Analysis of the model yields results on thresholds that would be necessary for a combined immune response to successfully control infection. Numerical simulations are presented to illustrate the results. These findings have the potential to lead to immunological control measures for lentiviral infection.
基金supported by grants from the National Natural Science Foundation of China (32172831 and 31672578 to XF.W,32170169 to X.W)the Postdoctoral Scientific Research Developmental Fund of Heilongjiang Province (LBH-Q20059 to XF.W)the Central Public-interest Scientific Institution Basal Research Fund (1610302022007 to XF.W).
文摘Equine infectious anemia virus(EIAV)is a member of the lentivirus genus in the Retroviridae family and is considered an animal model for HIV/AIDS research.An attenuated EIAV vaccine,which was successfully developed in the 1970s by classical serial passage techniques,is the first and only lentivirus vaccine that has been widely used to date.Restriction factors are cellular proteins that provide an early line of defense against viral replication and spread by interfering with various critical steps in the viral replication cycle.However,viruses have evolved specific mechanisms to overcome these host barriers through adaptation.The battle between the viruses and restriction factors is actually a natural part of the viral replication process,which has been well studied in human immunodeficiency virus type 1(HIV-1).EIAV has the simplest genome composition of all lentiviruses,making it an intriguing subject for understanding how the virus employs its limited viral proteins to overcome restriction factors.In this review,we summarize the current literature on the interactions between equine restriction factors and EIAV.The features of equine restriction factors and the mechanisms by which the EIAV counteract the restriction suggest that lentiviruses employ diverse strategies to counteract innate immune restrictions.In addition,we present our insights on whether restriction factors induce alterations in the phenotype of the attenuated EIAV vaccine.
基金This work was supported in part by the National Natural Science Foundation of China (Grant No. 39470535) the Excellent Youth Science Foundation of Heilongjiang Province.
文摘Proviral DNA was extracted from donkey leukocyte infected with Chinese donkey leukocyte attenuated equine infectious anemia virus(DLA-EIAV), and peripheral blood lymphocytes(PBL) from a horse infected with the virulent EIAV strain Liaoning(EIAV L). The entire proviral DNA from both viruses was cloned and sequenced. The lengths of complete genomic sequences of DLA-EIAV and EIAV L provirus were 8266 bp and 8235 bp, respectively. Sequence comparison indicated that DLA-EIAV shares 97.0% and 97.5% in sequence homology with EIAV L and donkey-adapted EIAV(DA-EIAV), respectively. Lots of variations occurred in long terminal repeat(LTR, consisting of U3, R, U5), ORF S2, and env regions between DLA-EIAV and EIAV L. The nucleotide sequence differences of the two viruses in U3, R, U5, ORF S2, and env are 13.2%, 7.5%, 5.1%, 3.9%, and 2.7%, respectively, and predicted amino acid sequence differences in env and S2 coding regions are 4.4% and 8.8%, respectively. Six conserved regions are characterized in Gp90. There is a cis-activating GATA motif in ENH of DLA-EIAV and EIAV L. Two N-linked glycosylation sites disappeared in DLA-EIAV Gp90 in comparison with that of EIAV L. A bHLH transcription factor binding consensus sequence was found in LTR of DLA-EIAV but not in EIAV L. Furthermore, there is a mutation in the stem of DLA-EIAV TAR resulting in formation of a uridine tuber. Further study is needed to uncover the relationship between sequence changes and their biological functions of DLA-EIAV and L.
