Table 2.
Influenza A(H3N2) Phylogenetic Subclusters by Season, Canadian Sentinel Practitioner Surveillance Network 2016–2017 and 2017–2018
| Parent Groups With Defining Substitutions [Antigenic Site]a + Extra Substitutions [Antigenic Site]b | 2016–2017, n (%), N = 574 | 2017–2018, n (%), N = 620 |
|---|---|---|
| 3C.2a = 3C.2c+ L3I + N144S [A] + F159Y [B] + K160T [B] (+CHO) + N225D (RBS) + Q311H [C]d | 7 (1) | 1 (<1) |
| +T131K [A] + R142K [A]e | 5 | − |
| 3C.2a1 = 3C.2a + N171K [D]f | 38 (7) | − |
| + S47T [C] + G78S [E] | 14 | − |
| + R142G [A] | 10 | − |
| 3C.2a1 + N121K [D] | 5 (1) | − |
| + R142K [A] | 1 | |
| 3C.2a1 + N121K [D] + I140M [A] g | 7 (1) | − |
| 3C.2a1 + N121K [D] + R142G [A] | 94 (16) | − |
| + T135K [A] (RBS) (−CHO) | 16 | − |
| 3C.2a1 + N121K [D] + R142G [A] + I242V [D] g | 113 (20) | − |
| 3C.2a1a = 3C.2a1 + N121K [D] + T135K [A] (RBS) (−CHO)g | 93 (16) | 5 (1) |
| + T167S [D] (−CHO) | 19 | − |
| + N96S [D] | 17 | − |
| + S46T [C] (−CHO) | 8 | − |
| 3C.2a1b = 3C.2a1 + N121K [D] + K92R [E] + H311Q [C] | 73 (13) | 34 (5) |
| + Q197R [B] | 57 | 3 |
| + E62G [E] + T135K [A] (RBS) (−CHO) + R142E [A] h | − | 3 |
| + E62G [E] + T135K [A] (RBS) (−CHO) + R142G [A]g | − | 25 |
| + E62G [E] + R142G [A] | − | 1 |
| 3C.2a2 = 3C.2a + T131K [A] + R142K [A] + R261Q [E]i | 81 (14) | 540 (87) |
| + F193S [B] | 20 | 2 |
| + R201K [D] | 11 | 6 |
| + H156Q [B] | 6 | − |
| + A212T [D]j | − | 170 |
| + K92R [E]k | − | 67 |
| + S144R [A] | − | 10 |
| + T160K [B] (−CHO) | − | 11 |
| + Y94H [E] | − | 9 |
| 3C.2a3 = 3C.2a + N121K [D] + S144 K [A] | 41 (7) | 10 (2) |
| + S219Y [D] | 30 | − |
| + T135K [A] (RBS) (−CHO) + R150K [A] + R261Q [E] | − | 9 |
| 3C.2a4 = 3C.2a + N31S + D53N [C] + R142G [A] + S144R [A] + N171K [D] + I192T [B] + Q197H [B] | 1 (<1) | 3 (<1) |
| 3C.3a = 3C.3l+ A138S [A] (RBS) + F159S [B] + N225D (RBS) + K326Rm | 21 (4) | 27 (4) |
| + L3I + S91N [E] + N144K [A] (−CHO) + F193S [B]n, o | 20 | 27 |
Abbreviations: +/− CHO, gain/loss of potential N-linked glycosylation site; RBS, substitutions within the receptor binding site; "−" indicates not detected.
aParent genetic groups with their defining hemagglutinin (HA) substitutions and number of viruses are shown in bold font. The number of viruses with additional specified substitutions are shown in normal font. Substitutions are for HA1 unless specified as for HA2. Clades 3C.2a, 3C.2a1, 3C.2a1a, 3C.2a1b, 3C.2a2, 3C.2a3, 3C.2a4, and 3C.3a are well-recognized parent groupings [11–13, 17]. Additional 3C.2a1 parent groups specified here are based on phylogenetic analysis, additionally informed by published sources [22, 23]. Not all substitutions or potential subclusters are displayed; for additional details see phylogenetic trees in Supplementary Figure 5A and 5B. Note that the vaccine strain each season was clade 3C.2a.
bExtra substitutions in antigenic sites of at least 1% of all viruses either season are shown. The tally with T131K [A], T135K [A], or R142G/K/E [A] are also shown.
cClade 3C.2 defined by 3C + N145S [A] + HA2: D160N.
dAll clade 3C.2a viruses are also S96N [D], K160T [B] (+CHO) and P194L [B] (RBS) relative to the egg-adapted 3C.2a vaccine (ie, the latter is 96S, 160K, and 194P).
eOf these clade 3C.2a viruses bearing T131K [A] + R142K [A] substitutions, one also bears A212T [D] but none bear R261Q [E], the latter clade defining for 3C.2a2.
fClade 3C.2a1 defining substitutions additionally include HA2: G155E and HA2: I77V.
gAdditional defining substitution includes HA2: G150E.
hIn 2017–2018, one other 3C.2a1b virus bore T135N [A] (RBS) (−CHO). No 3C.2a1b virus bore T131K [A], subsequently prominent among 3C.2a1b viruses in 2018–2019 [11–13].
iAdditional substitutions enumerated for clade 3C.2a2 are not mutually exclusive. Two 3C.2a2 viruses in 2017–2018 are K142R. Further subclusters of clade 3C.2a2 have not been defined by published sources to date [11–13].
jIn 2017–2018, 8/170 of these viruses form a potential subcluster; the remainder are distributed and/or cluster phylogenetically with viruses that lack A212T [D].
kIn 2017–2018, 66/67 of these viruses form a potential subcluster.
lClade 3C.3 defined by 3C + T128A[B](−CHO) + R142G [A] + N145S[A].
mRelative to the clade 3C.2a vaccine strain, clade 3C.3a viruses are I3L, S144N [A], Y159S (rather than F159S owing to clade-defining F159Y substitution in 3C.2a viruses), H311Q [C], and HA2: N160D, but no longer N145S [A] and N225D (RBS) as a result of parallel substitutions in the 3C.2a vaccine strain (ie, the vaccine strain is also 145S and 225D). All clade 3C.3a viruses are also S96N [D] and P194L [B] (RBS) relative to the egg-adapted clade 3C.2a vaccine strain (ie, the egg-adapted vaccine is 96S and 194P). Unlike clade 3C.2a viruses, clade 3C.3a viruses are 160K (nonglycosylated), as is the egg-adapted clade 3C.2a vaccine strain.
nThese clade 3C.3a viruses are also HA2: D160N.
oRelative to the clade 3C.2a vaccine strain, these clade 3C.3a viruses are S144K (rather than N144K owing to N144S substitution in 3C.2a viruses) and no longer possess I3L and HA2: N160D (from footnote n) as a result of parallel substitutions in the 3C.2a vaccine strain (ie, the vaccine strain is 3I and HA2: 160N).