NOVEL PATTERNS OF THE EPSTEIN-BARR NUCLEAR
ANTIGEN (EBNA-1) V-VAL SUBTYPE IN EBV-ASSOCIATED
NASOPHARYNGEAL CARCINOMA FROM VIETNAM
Thuan LD1, Kha ND2, Minh NT3, Thuy LHA1,*
*Corresponding Author: Thuy Le Huyen Ai, Ph.D., Associate Professor, Department of Pharmaceutical
and Medical Biotechnology, Faculty of Biotechnology, Room 304, 97 Vo Van Tan Street, Ward 6, District 3,
Ho Chi Minh City Open University, Ho Chi Minh City, Vietnam.
Tel: +84-905-784-471. E-mail: thuy.lha@ ou.edu.vn
page: 61
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RESULTS
V-Val EBNA-1 Subtype was Preferential in Vietnamese
Nasopharyngeal Cancer. The C-terminal domain
of EBNA-1 was successfully amplified, observed in a distinct band with 745 bp (shown in Figure 2) and sequenced
in 44 of 58 clinical samples, accounting for 75.86%. The
nucleotide variations were identified by comparison with
the B95-8 P-Ala sequence. The sequencing results showed
that P-Ala, P-Thr, V-Val and V-Leu were identified based
on the amino acid at position 487 (Figure 3). The proportion
of P-Ala, P-Thr, V-Val and V-Leu were two of 44
cases (accounting for 4.55%), five of 44 cases (accounting
for 11.36%), 35 of 44 cases (accounting for 79.55%)
and two of 44 cases (accounting for 4.55%), respectively.
Thus, it was concluded that the V-Val EBNA-1 subtype
was the common subtype, and V-Pro was not detected in
Vietnamese nasopharyngeal cancer.
Characteristic of V-Val Sequence patterns of
EBNA-1 in Vietnamese Nasopharyngeal Cancer. All
the nucleotide variants of sequence, encoded the amino
acid residue 487 of the EBNA-1 C-terminal domain, 35
cases of V-Val EBNA-1 were determined by comparison
with the B95-8 sequence. As a result, five patterns of VVal
subtype of EBNA-1 C-terminal domain, coded pattern
1 to pattern 5, were identified (Table 2). All of those five
patterns contained seven consensus changes, including five
amino acid changes and two silent changes (Figure 4). The
five amino acid changes were at residue 487 (Ala→Val;
GCT>GTT), 499 (Asp→Glu; GAC>GAG), 502 (Thr→
Asn; ACT>AAT), 524 (Thr→Ile; ACT>ATT), 594 (Arg→
Lys; AGG>AAG). The two silent amino acid changes were
at residue 520 (Leu→Leu; CTA>CTC) and 553 (Pro→Pro;
CCG>CCA). In the V-Val subtype, pattern isolates showed
two or more additional changes except for the consensus
sequence changes (Figure 5). There were pattern 1: 17 of
35 isolates (accounting for 48.57%, represented by T5)
with additional amino changes at residue 528 (Ile→Val;
ATT>GTT), 533 (Leu→Ile; CTT>ATT); pattern 2: 14 of
35 isolates (accounting for 40.00%, represented by T6)
with additional substitutions at residue 528 (Ile→Val;
ATT>GTT), 533 (Leu→Ile; CTT>ATT), 585 (Thr→Ile;
ACA>ATA); pattern 3: 2 of 35 isolates (accounting for
5.71%, represented by T77) with additional changes at
residue 529 (Pro→Gln; CCA>CAA), 585 (Thr→Ile;
ACA>ATA), 588 (Ala→Pro; GCT>CCT); pattern 4:
one of 35 isolates (accounting for 2.86%, represented by
T70) with additional changes at amino acid 528 (Ile→Val;
ATT>GTT), 533 (Leu→Ile; CTT>ATT), 585 (Thr→Ile;
ACA>ATA), 588 (Ala→Pro; GCT>CCT); pattern 4: one
of 35 isolates (accounting for 2.86%, represented by T75)
with additional amino acid changes at position 492 (Ser→
Cys; AGT>TGT), 528 (Ile→Val; ATT>GTT), 533 (Leu→
Ile; CTT>ATT), 585 (Thr→Ile; ACA>ATA), 588 (Ala→
Pro; GCT>CCT). Therefore, the common pattern of V-Val
subtypes were pattern 1 (accounting for 48.57%) and pattern
2 (accounting for 40.00%). Novel Patterns of V-Val Subtype of the EBNA-
1 C-Terminal Domain from Vietnamese Patients. The
previous study of Wang et al. [19] reported that the common
pattern of EBNA-1 C-terminal domain contained 12
consensus sequence changes, including 10 amino acid
changes at positions 487, 499, 502, 524, 528, 533, 594,
and two silent changes at residues 520 and 553. Additionally,
those 12 consensus sequence changes were reported
to be the same as the sequences of published V-Val subtype
or its sub-variants at the sequenced part in previous studies
[13,15,20-23]. Compared to our study, 10 amino acid at positions
487, 499, 502, 520, 524, 553 and 594 were the same
as the GC4 (Table 3). The amino acid at positions 528 and
533 were different to the consensus amino acid of the GC4
sequence. Moreover, besides the consensus substitutions,
which were reported in GC4, in our patterns of EBNA-1
variants, the amino acid at position 492 (Ser→ Cys) by
T75, 528 (without change: Ile); 529 (Pro→Gln); 553 (with
change: Leu) by T77; 585 (Thr→Ile) by T6, T77, T70, T75;
and 588 (Ala→Pro) by T77, T70, T75, were different to
GC4 (Table 3). Therefore, it could be concluded that pattern
1 (represented by T5) was the same as the GC4. Pattern 2
(represented by T6), pattern 3 (represented by T77), pattern
4 (represented by T70), and pattern 5 (represented by T75)
were different to GC4, thus, identified as the novel patterns
of EBNA-1 C-terminal domain in Vietnamese NPC.
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