Limits...
Hepatitis C Virus Core Mutations Associated with False-Negative Serological Results for Genotype 3a Core Antigen.

Nguyen LT, Dunford L, Freitas I, Holder P, Nguyen LA, O'Gorman J, Connell J, Carr M, Hall W, De Gascun C - J. Clin. Microbiol. (2015)

Bottom Line: Genetic characterization of the genotype 3a (GT3a) hepatitis C virus (HCV) core region from HCV core antigen (HCVcAg)-negative/RNA-positive cases and HCVcAg-positive/RNA-positive controls identified significant associations between the substitutions A48T and T49A/P and failure to detect HCVcAg (P < 0.05).Polymorphisms at residues 48 and 49 in the core protein are present across all major epidemic and endemic GTs.These findings have implications for HCV diagnosis, particularly in low-income regions in which GT3a HCV is endemic.

View Article: PubMed Central - PubMed

Affiliation: Ireland Vietnam Blood-Borne Virus Initiative, Dublin, Ireland, and Hanoi, Vietnam Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin, Belfield, Ireland Laboratory for Molecular Diagnostics, National Institute of Hygiene and Epidemiology, Hanoi, Vietnam crid.office@ucd.ie.

No MeSH data available.


Related in: MedlinePlus

Amino acid sequence alignment (160 residues) of the mature GT3a HCV core protein, showing comparison of sequences derived from controls (n = 36) and cases (n = 7). Amino acid positions in the HCV core protein are numbered, and sequence identity is represented by single dots. Red box, region including residues 48 and 49, which were significantly associated with compromised HCVcAg measurements. X, presence of more than one amino acid.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4508445&req=5

Figure 2: Amino acid sequence alignment (160 residues) of the mature GT3a HCV core protein, showing comparison of sequences derived from controls (n = 36) and cases (n = 7). Amino acid positions in the HCV core protein are numbered, and sequence identity is represented by single dots. Red box, region including residues 48 and 49, which were significantly associated with compromised HCVcAg measurements. X, presence of more than one amino acid.

Mentions: Genetic characterization of the core gene in GT3a HCV false-negative cases and controls determined amino acid substitutions associated with the underquantification of HCVcAg. A48T was found in 5.5% of controls (2/36 samples) versus 42.9% of cases (3/7 samples) (P < 0.05). T49A/P was found in 8.3% of controls (3/36 samples) versus 42.9% of cases (3/7 samples) (P < 0.05). The alignment of 160 amino acid residues in the core region of 36 controls and seven cases is shown in Fig. 2. For case 7, substitutions at residues 48 and 49 were absent, but we noted the presence of L44M; this mutation was not seen in other sequences from either cases or controls (Fig. 2). In the Los Alamos database, L44 predominates in all HCV GTs (range, 98.58 to 100%) and is present in 100% of GT3a sequences, which indicates the relative rarity of L44M. Consequently, this mutation may also affect the ability of the monoclonal antibodies in the assay to detect HCVcAg.


Hepatitis C Virus Core Mutations Associated with False-Negative Serological Results for Genotype 3a Core Antigen.

Nguyen LT, Dunford L, Freitas I, Holder P, Nguyen LA, O'Gorman J, Connell J, Carr M, Hall W, De Gascun C - J. Clin. Microbiol. (2015)

Amino acid sequence alignment (160 residues) of the mature GT3a HCV core protein, showing comparison of sequences derived from controls (n = 36) and cases (n = 7). Amino acid positions in the HCV core protein are numbered, and sequence identity is represented by single dots. Red box, region including residues 48 and 49, which were significantly associated with compromised HCVcAg measurements. X, presence of more than one amino acid.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4508445&req=5

Figure 2: Amino acid sequence alignment (160 residues) of the mature GT3a HCV core protein, showing comparison of sequences derived from controls (n = 36) and cases (n = 7). Amino acid positions in the HCV core protein are numbered, and sequence identity is represented by single dots. Red box, region including residues 48 and 49, which were significantly associated with compromised HCVcAg measurements. X, presence of more than one amino acid.
Mentions: Genetic characterization of the core gene in GT3a HCV false-negative cases and controls determined amino acid substitutions associated with the underquantification of HCVcAg. A48T was found in 5.5% of controls (2/36 samples) versus 42.9% of cases (3/7 samples) (P < 0.05). T49A/P was found in 8.3% of controls (3/36 samples) versus 42.9% of cases (3/7 samples) (P < 0.05). The alignment of 160 amino acid residues in the core region of 36 controls and seven cases is shown in Fig. 2. For case 7, substitutions at residues 48 and 49 were absent, but we noted the presence of L44M; this mutation was not seen in other sequences from either cases or controls (Fig. 2). In the Los Alamos database, L44 predominates in all HCV GTs (range, 98.58 to 100%) and is present in 100% of GT3a sequences, which indicates the relative rarity of L44M. Consequently, this mutation may also affect the ability of the monoclonal antibodies in the assay to detect HCVcAg.

Bottom Line: Genetic characterization of the genotype 3a (GT3a) hepatitis C virus (HCV) core region from HCV core antigen (HCVcAg)-negative/RNA-positive cases and HCVcAg-positive/RNA-positive controls identified significant associations between the substitutions A48T and T49A/P and failure to detect HCVcAg (P < 0.05).Polymorphisms at residues 48 and 49 in the core protein are present across all major epidemic and endemic GTs.These findings have implications for HCV diagnosis, particularly in low-income regions in which GT3a HCV is endemic.

View Article: PubMed Central - PubMed

Affiliation: Ireland Vietnam Blood-Borne Virus Initiative, Dublin, Ireland, and Hanoi, Vietnam Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin, Belfield, Ireland Laboratory for Molecular Diagnostics, National Institute of Hygiene and Epidemiology, Hanoi, Vietnam crid.office@ucd.ie.

No MeSH data available.


Related in: MedlinePlus