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Genomic Changes in an Attenuated ZB Strain of Foot-and-Mouth Disease Virus Serotype Asia1 and Comparison with Its Virulent Parental Strain.

Xin A, Zhu M, Peng Z, Hu Q, Shi C, Liao D, Wang J, Li H - Int J Genomics (2014)

Bottom Line: To understand the genetic changes of attenuation, we compared the entire genomes of three different rabbit-passaged attenuated ZB strains (ZB/CHA/58(att), ZBRF168, and ZBRF188) and their virulent parental strains (ZBCF22 and YNBS/58).The results showed that attenuation may be brought about by 28 common amino acid substitutions in the coding region, with one nucleotide point mutation in the 5'-untranslated region (5'-UTR) and another one in the 3'-UTR.In addition, a total of 21 nucleotides silent mutations had been found after attenuation.

View Article: PubMed Central - PubMed

Affiliation: Yunnan Tropical and Subtropical Animal Virus Disease Laboratory, Yunnan Animal Science and Veterinary Institute, Kunming 650224, China.

ABSTRACT
The molecular basis of attenuation of foot-and-mouth disease virus (FMDV) serotype Asia1 ZB strain remains unknown. To understand the genetic changes of attenuation, we compared the entire genomes of three different rabbit-passaged attenuated ZB strains (ZB/CHA/58(att), ZBRF168, and ZBRF188) and their virulent parental strains (ZBCF22 and YNBS/58). The results showed that attenuation may be brought about by 28 common amino acid substitutions in the coding region, with one nucleotide point mutation in the 5'-untranslated region (5'-UTR) and another one in the 3'-UTR. In addition, a total of 21 nucleotides silent mutations had been found after attenuation. These substitutions, alone or in combination, may be responsible for the attenuated phenotype of the ZB strain in cattle. This will contribute to elucidation of attenuating molecular basis of the FMDV ZB strain.

No MeSH data available.


Related in: MedlinePlus

Comparison of amino acid differences between the ZB virulent and attenuated strains: (a) VP1 antigen site B (aa130-160) and (b) 3A (aa76-127).
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Related In: Results  -  Collection


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fig3: Comparison of amino acid differences between the ZB virulent and attenuated strains: (a) VP1 antigen site B (aa130-160) and (b) 3A (aa76-127).

Mentions: The highest mutation rate was found in the VP1 protein with eight amino acid substitutions during the attenuation process of the ZB strains (Table 3). Four of them (A4-T, P45-L, A81-V, and S147-A) included amino acids with similar nature, while two others (A21-E and S142-R) resulted in a change of amino acids charge. It was previously proposed that changes of viral surface may play an important role in attenuation process. Therefore, VP1 is likely to be the protein for attenuating mutations. Indeed, a recent study demonstrated that the capsid proteins of the O1Kaubeuren B64 strain were responsible for its attenuation in cattle [35]. Moreover, the adaptive replacement of L147-P in VP1 of the guinea pig-adapted C-S8c1 strain abolished growth of the virus in different established cell lines and modified its antigenicity [36]. Additionally, substitution of D143-A in the G-H loop antigenic site (VP1 residues 138 to 150) abolished infectivity of virus in suckling mice [37]. After ZB strain attenuation, the influence of the S142-R change in the −1 position and S147-A change in the +2 position of RGD is not clear (Figure 3(a)). The amino acid substitutions around the RGD motif suggest advantages of these substitutions in host cell recognition and binding during the attenuation process of the ZB strains. It is conceivable that these amino acid substitutions may modify the surface properties of the virion in a way that may reduce its virulence in cattle. The amino acids immediately following the RGD motif have a major influence on the ability of the different integrin species, and RGD +1 position is important in the receptor recognition process [38]. Residue phenylalanine at RGD +1 position of the cell-adapted rabbit-attenuated ZB/CHA/58(att) was different in other ZB strains, suggesting that this substitution may be associated with the cell adaptation in BHK-21 cells.


Genomic Changes in an Attenuated ZB Strain of Foot-and-Mouth Disease Virus Serotype Asia1 and Comparison with Its Virulent Parental Strain.

Xin A, Zhu M, Peng Z, Hu Q, Shi C, Liao D, Wang J, Li H - Int J Genomics (2014)

Comparison of amino acid differences between the ZB virulent and attenuated strains: (a) VP1 antigen site B (aa130-160) and (b) 3A (aa76-127).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4216683&req=5

fig3: Comparison of amino acid differences between the ZB virulent and attenuated strains: (a) VP1 antigen site B (aa130-160) and (b) 3A (aa76-127).
Mentions: The highest mutation rate was found in the VP1 protein with eight amino acid substitutions during the attenuation process of the ZB strains (Table 3). Four of them (A4-T, P45-L, A81-V, and S147-A) included amino acids with similar nature, while two others (A21-E and S142-R) resulted in a change of amino acids charge. It was previously proposed that changes of viral surface may play an important role in attenuation process. Therefore, VP1 is likely to be the protein for attenuating mutations. Indeed, a recent study demonstrated that the capsid proteins of the O1Kaubeuren B64 strain were responsible for its attenuation in cattle [35]. Moreover, the adaptive replacement of L147-P in VP1 of the guinea pig-adapted C-S8c1 strain abolished growth of the virus in different established cell lines and modified its antigenicity [36]. Additionally, substitution of D143-A in the G-H loop antigenic site (VP1 residues 138 to 150) abolished infectivity of virus in suckling mice [37]. After ZB strain attenuation, the influence of the S142-R change in the −1 position and S147-A change in the +2 position of RGD is not clear (Figure 3(a)). The amino acid substitutions around the RGD motif suggest advantages of these substitutions in host cell recognition and binding during the attenuation process of the ZB strains. It is conceivable that these amino acid substitutions may modify the surface properties of the virion in a way that may reduce its virulence in cattle. The amino acids immediately following the RGD motif have a major influence on the ability of the different integrin species, and RGD +1 position is important in the receptor recognition process [38]. Residue phenylalanine at RGD +1 position of the cell-adapted rabbit-attenuated ZB/CHA/58(att) was different in other ZB strains, suggesting that this substitution may be associated with the cell adaptation in BHK-21 cells.

Bottom Line: To understand the genetic changes of attenuation, we compared the entire genomes of three different rabbit-passaged attenuated ZB strains (ZB/CHA/58(att), ZBRF168, and ZBRF188) and their virulent parental strains (ZBCF22 and YNBS/58).The results showed that attenuation may be brought about by 28 common amino acid substitutions in the coding region, with one nucleotide point mutation in the 5'-untranslated region (5'-UTR) and another one in the 3'-UTR.In addition, a total of 21 nucleotides silent mutations had been found after attenuation.

View Article: PubMed Central - PubMed

Affiliation: Yunnan Tropical and Subtropical Animal Virus Disease Laboratory, Yunnan Animal Science and Veterinary Institute, Kunming 650224, China.

ABSTRACT
The molecular basis of attenuation of foot-and-mouth disease virus (FMDV) serotype Asia1 ZB strain remains unknown. To understand the genetic changes of attenuation, we compared the entire genomes of three different rabbit-passaged attenuated ZB strains (ZB/CHA/58(att), ZBRF168, and ZBRF188) and their virulent parental strains (ZBCF22 and YNBS/58). The results showed that attenuation may be brought about by 28 common amino acid substitutions in the coding region, with one nucleotide point mutation in the 5'-untranslated region (5'-UTR) and another one in the 3'-UTR. In addition, a total of 21 nucleotides silent mutations had been found after attenuation. These substitutions, alone or in combination, may be responsible for the attenuated phenotype of the ZB strain in cattle. This will contribute to elucidation of attenuating molecular basis of the FMDV ZB strain.

No MeSH data available.


Related in: MedlinePlus