Detection of an Amino Acid Substitution
That Inhibits Secretion of HBV SVPs
Intervirology 2008;51:81–86
85
The unique amino acid variation observed here, from
leucine to glutamine (L215Q) in the carboxyl-terminal
end of S-HBsAg of an HBV genotype F isolate, was re-
sponsible for a considerable inhibition of SVP secretion.
It is well known that mutated proteins that are not se-
creted can cause stress in the ER, affecting cellular tran-
scription via intracellular signaling pathways
[22, 23] . In
transgenic mice, inhibition of HBsAg secretion has been
related to the occurrence of cell injury mediated by inter-
feron- ␥
[24] . Furthermore, an association has been pro-
posed between HBsAg secretion inhibition and occult
HBV infection
[25] . Among 1,220 HBV sequences avail-
able in databanks, only two (sequence accession numbers
AY311358 [genotype F] and AF090842 [genotype A]) ex-
hibited an amino acid variation at residue 215. In both of
them, however, the substitution, from leucine to valine,
was conservative. The presence of charged or polar ami-
no acids in a TM segment has been shown to be crucially
involved in ER retention
[26, 27] . A previous study has
shown that a deletion of amino acid residues 214–218, and
replacement by a positively charged Lys residue, resulted
in deficient secretion of SVPs
[15] . Here, the substitution
of a nonpolar Leu residue by the strongly polar Gln at the
center (position 215) of TM4 segment may affect the con-
formation of HBsAg, possibly leading to defective inser-
tion into the ER membrane and intracellular retention.
Our present findings highlight the effect on SVP secre-
tion of amino acid substitutions in the carboxyl-terminal
end of S-HBsAg, other than those previously described
in the amino-terminal end of the protein as well as in the
antigenic loop
[11, 12, 14] .
Acknowledgements
We gratefully acknowledge Prof. C. Trepo and Dr. A. Kay for
providing HuH7 cells and Dr. C. Niel for helpful discussions. This
work was supported by Conselho Nacional de Desenvolvimento
Científico e Tecnológico (CNPq).
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