First Hong Kong Human Case, 36F, Repeats H3N2 Antigenic HA 128A

Sequences discussed in this analysis are variously stored publicly at GenBank and at GISAID. We gratefully acknowledge the authors, originating and submitting laboratories of the sequences from GenBank and from GISAID’s EpiFlu™ Database on which this research is based. A GISAID-generated list is detailed in a linked Excel for completeness in citation.

Publish Date : 2013-12-05
Last Update : 2014-04-07

On 2013-12-04, the Centre for Health Protection of Hong Kong released a full set of sequences at GISAID from the most recent Emergent H7N9 human case.  The 36 year old female domestique was sampled in Hong Kong on 2013-11-30 during hospitalisation.  She was variously reported to be from Indonesia and India, although the Indonesian consulate has confirmed her nationality at this time.  Emergent H7N9 went undetected on the first two Influenza tests

Four home contacts and a patient who shared a ward at Tuen Mun Hospital have exhibited symptoms.  Twelve Health Care Workers who attended the patient have also exhibited symptoms.

The Emergent H7N9 human reservoir once again displays fecundity with yet another novel constellation of ReAssortment gaining internal genes from the H9N2 reservoir, including all three of the Polymerase Complex (Segments 1,2,3). Within this Polymerase Complex, only segment 1, PB2, resembles the previous human ReAssortment from Guangdong, notably at a distance of 8 residues.  Hypermorphic behaviour is certainly now in evidence from this host-transition reservoir.

HA 128A repeats on this second reported Emergent H7N9 sequence with an epidemiological relationship to Guangdong province, i.e. GuangdongHuizhou1_51F_2013_08_10_s.  This HA 128A antigenic variation is currently circulating world-wide from the Season 2012 Human H3N2 reservoir (Record-Setting Fatalities and Hospitalisations).  HA 128A features on the Russian sequence from the recent GeneWurx H3N2 dual geography Prediction Validation report concerning another potential antigenic site revision.

A comprehensive collection of official reports and journalists' filings covering the events surrounding this latest human Emergent H7N9 case may be accessed at the crowd-sourced, FluTrackers forum [214444] thread.  Hong Kong Department of Health reports are in evidence, including descriptions of multiple diagnostic testing failures while influenza symptoms were present in this patient, in the patient's employers and in hospital contacts of the patient.  This Hong Kong index patient is indicated as Case #142 on the 2013 H7N9 Human Case List maintained by the FT moderator and forum members. Due to testing irregularities, no other cases are presently H7N9-confirmed in these multiple symptomatic clusters having a shared focus.

Activity tracing relates recent travel by the patient to the mainland, specifically Shenzhen, Guangdong, on November 17^th.  Bloomberg reports that Hong Kong residents log more than 30 million trips each year to the popular Shenzhen day-trip destination. Dr. Ian Mackay (University of Queensland), H7N9 Visualiser, adroitly describes viral spread proclivity in the Bloomberg article and at his publication center, Virology Down Under, Editor's Note #12:

“Respiratory viruses do their own thing; they don’t respect boundaries,” said Ian Mackay, an associate professor of clinical virology at the University of Queensland in Brisbane, Australia, in a telephone interview. “It does seem that it’s continuing to add to provinces and regions, rather than reappear in all the old places it started in back in February and March.”

Although the first Hong Kong human case sequence does resemble the first Guangdong human case sequence on the HA and loosely on a similar, but certainly not matching, H9N2-like PB2, HongKong5942_M_36F_2013_11_30_s manifests a distinct segment constellation with variant H9N2-like PA and PB1 segments.  A novel polymorphism to Emergent H7N9 also arises on the Neuraminidase, NA 264V.  That NA revision has been found co-located on pH1N1 sequences with HA 230I.

With HA 128A, an H3N2 human seasonal circulation, appearing to fix over the course of three months and the novelty of NA 264V, a human  pH1N1 revision, the Hong Kong case gains human-hosted genetics and potentially functional infectivity.  The fresh Polymerase complex is suggestive that reassortment comes with ease for these current H7N9 genetics.  After noting that H5N1 acquired a full Polymerase complex from Emergent H7N9 during early April 2013 in presumable Wet Market Surveillance at Hangzhou, Zhejiang Province, we began to understand the attractant allegiance these cross-group reservoirs share.

What GeneWurx had originally marked as mere fealty is now documented as practical sycophantic bi-directionality.

At any estimation, diagnostic testing was eluded successfully in many cases on this particular background.  Potential involvement of two circulating human disease reservoirs as donors (pH1N1 & sH3N2) increases the risk of silent spread leading to wider human morbidity.

HA Polymorphisms

. . . . HongKong5942_M_36F_2013_11_30_s (

. . . . . . . . A/Hong Kong/5942/2013

. . . . . . . . Clinical: 2013-11-21 Cough
. . . . . . . . Clinical: 2013-11-25 Sought Medical Assistance, Private Doctor
. . . . . . . . Clinical: 2013-11-27 Shortness of Breath, Tuen Mun Hospital Admission
. . . . . . . . Clinical: 2013-11-29 Tuen Mun Hospital Critical Care
. . . . . . . . Clinical: 2013-11-30 Queen Mary Hospital Transfer
. . . . . . . . Clinical: 2013-12-07 ECMO complete, Oxygen Continues
. . . . . . . . Clinical: 2013-12-07 Oxygen continues
. . . . . . . . Clinical: 2013-12-07 Remains in Critical Care

. . . . . . . . Clinical Tx: ECMO

. . . . . . . . GISAID HA EPI490882

. . . . . . . . GISAID Isolate EPI_ISL_151417

. . . . . . . . 104 Polymorphisms (19 Amino and 85 Silent)

. . . . . . . . 11I [#4I] [zH3N2],

. . . . . . . . 130A [118A],

. . . . . . . . 140A [128A] [H3N2 Human Seasonal],

. . . . . . . . 183S [174S] [zH3N2],

. . . . . . . . 188V [179V] [zH3N2],

. . . . . . . . 195V [186V],

. . . . . . . . 198A [189A],

. . . . . . . . 211V [202V] [zH3N2],

. . . . . . . . 217N [208N],

. . . . . . . . 235L [226L] [zH3N2],

. . . . . . . . 285N [277N] [zH3N2],

. . . . . . . . 300S [292S],

. . . . . . . . 307D [299D],

. . . . . . . . 321R [313R] [H9N2],

. . . . . . . . 410N [401N],

. . . . . . . . 427I [418I],

. . . . . . . . 455D [446D],

. . . . . . . . 462K [453K] [zH3N2],

. . . . . . . . 541V [533V])

NA Polymorphisms

. . . . HongKong5942_M_36F_2013_11_30_s (

. . . . . . . . A/Hong Kong/5942/2013
. . . . . . . . Novel Neuraminidase

. . . . . . . . GISAID NA EPI490881

. . . . . . . . GISAID Isolate EPI_ISL_151417

. . . . . . . . 33 Polymorphisms (11 Amino and 22 Silent)

. . . . . . . . NA Truncated before aa10 [NA Truncated before aa10],

. . . . . . . . 16I [16I],

. . . . . . . . 19A [19A],

. . . . . . . . 40G [40G],

. . . . . . . . 53T [53T],

. . . . . . . . 81T [80T],

. . . . . . . . 84N [83N],

. . . . . . . . 112S [111S],

. . . . . . . . 264V [263V] [Emergent H7N9 Novel],
. . . . . . . . . . . . . . . . . [pH1N1 with HA 230I],
. . . . . . . . . . . . . . . . . [avH1N1_farm],
. . . . . . . . . . . . . . . . . [H5N1],
. . . . . . . . . . . . . . . . . [H6N1],

. . . . . . . . 335I [332I],

. . . . . . . . 359A [355A],

. . . . . . . . 401A [397A])

PB2 Polymorphisms

. . . . HongKong5942_M_36F_2013_11_30_s (

. . . . . . . . A/Hong Kong/5942/2013

. . . . . . . . ~ H9N2
. . . . . . . . Distant to Relative: Count 08 H7N9 Guangdong
. . . . . . . . Distant to Relative: Count 78 H7N9 Secondary
. . . . . . . . GISAID PB2 EPI490879

. . . . . . . . GISAID Isolate EPI_ISL_151417

. . . . . . . . 91 Polymorphisms (9 Amino and 82 Silent)

. . . . . . . . 139I [pH1N1 Rare: Early Emergence],

. . . . . . . . 191E [pH1N1 Wild Type],

. . . . . . . . 283I,

. . . . . . . . 286G,

. . . . . . . . 292I,

. . . . . . . . 559T,

. . . . . . . . 569A,

. . . . . . . . 570I,

. . . . . . . . 676V)

PB1 Polymorphisms

. . . . HongKong5942_M_36F_2013_11_30_s (

. . . . . . . . A/Hong Kong/5942/2013

. . . . . . . . ~ H9N2
. . . . . . . . Distant to Relative: Count 44 H5N1
. . . . . . . . Distant to Relative: Count 46 H7N9
. . . . . . . . Distant to Relative: Count 53 H7N9 Guangdong
. . . . . . . . GISAID PB1 EPI490880

. . . . . . . . GISAID Isolate EPI_ISL_151417

. . . . . . . . 46 Polymorphisms (4 Amino and 42 Silent)

. . . . . . . . 105H,

. . . . . . . . 178D,

. . . . . . . . 525I,

. . . . . . . . 682V)

PA Polymorphisms

. . . . HongKong5942_M_36F_2013_11_30_s (

. . . . . . . . A/Hong Kong/5942/2013

. . . . . . . . ~ H9N2
. . . . . . . . Distant to Relative: Count 58 H7N9
. . . . . . . . Distant to Relative: Count 74 H7N9 Guangdong
. . . . . . . . GISAID PA EPI490878

. . . . . . . . GISAID Isolate EPI_ISL_151417

. . . . . . . . 73 Polymorphisms (4 Amino and 69 Silent)

. . . . . . . . 100V,

. . . . . . . . 336M,

. . . . . . . . 356K [H5N1 Asia Human Fatalities], 

. . . . . . . . 394D)

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eH7N9 Influenza PolymeraseBasic2, PolymeraseBasic1, PolymeraseAcidic, Hemagglutinin & Neuraminidase Segments
elucidated at 2013-12-05-02_53_59_107890 by GeneWurx see.PolyDetector v0, Copyright 2007-2013.

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