Mutation in a Lordsdale Norovirus Epidemic Strain as a Potential Indicator of Transmission Routes

Kate E. Dingle

doi:10.1128/JCM.42.9.3950-3957.2004

DOI: 10.1128/JCM.42.9.3950-3957.2004

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FIG. 1.
Nucleotide sequences (285 nt) of the five closely related norovirus variants identified among 22 outbreaks (Table 1) and Lordsdale virus. The sequence is located within the RNA polymerase between primer pairs JV12Y and JV13I. Dots indicate sequence identity with variant 1. The 42 nt of primer sequence have been deleted from the 327-bp PCR amplicon. The locations of this sequence within the genome of strain Hu/NLV/Oxford/B5S22/2003/UK (GenBank accession no. AY581254) are indicated. The sequence equivalent to the 6-nt motif thought to indicate a new norovirus variant (16) is highlighted and boxed.
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FIG. 2.
Neighbor-joining tree showing relationships among 49 strains from 18 outbreaks within the 3′-terminal 3,255 nt. The strains and outbreaks are indicated as follows: hospital (Hosp), plus ward where more than one outbreak from one hospital was included; date of sample collection (month/day/year); and sample number. *, variants shed over 17 days by an immunocompromised patient.
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FIG. 3.
Relationships among capsid nucleotide sequences of eight of the Oxfordshire viruses, previous GII Lordsdale virus-like viruses, and other prototype noroviruses shown using a neighbor-joining tree. The input alignment file was generated using Clustal W version 1.8. The isolation years of the strains within the Lordsdale virus-like group are indicated with their corresponding clusters of variants. Bootstrap values are given at appropriate nodes. The GenBank accession numbers of the strains used are as follows: Dillingen/259/01/Germany, AF425766; Berlin/495/2000/Germany, AF427123; Koenigswusterhaus/120/2000/Germany, AF427121; 379/96019984/1996/Az, AF080556; 373/96019743/1996/SC, AF080555; Burwash Landing/331/1995/US, AF414425; 004/95 M-14/1995/AU, AF080551; Dijon171/1996/France, AF472623; Miami Beach/326/1995/US, AF414424; Berlin/238/98/Germany, AF425764; Beeskow/124/2000/Germany, AF427120; Oberschleissheim/112/1999/DE, AF427113; 416/97003156/1996/LA, AF 080559; Mora/1997/Sweden, AY081134; Parkroyal/1995/UK, AJ277613; Symgreen/1995/UK, AJ277619; Efurt/007/2000/Germany, AF427117; Hu/NV/Oxford/B5S22/2003/UK (a representative of the Oxfordshire viruses), AY581254; Bristol/1993/UK, X76716; UK3-17/12700/192/GB, AF414417; Lordsdale/1993/UK, X86557; Camberwell/1994/AU, AF145896; MD145-12/1987/US, AY032605; MD134-7/1987/US, AY030098; Toronto virus, U02030; Hawaii virus, U07611; Hillingdon virus, AJ277607; Snow Mountain virus, L23831; Melksham virus, X81879; Mexico virus, U22498; Desert Shield virus, U04469; Norwalk virus, M87661; and Southampton virus, L07418.
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FIG. 4.
Alignment of the capsid amino acid sequences of the representative Oxfordshire variant Hu/NV/Oxford/B5S22/2003/UK (GenBank AY581254), its closest previously described relative (004/95 M-14/1995/AU [GenBank AF080551]), and Norwalk virus (GenBank M87661). The different subdomains of the capsids, estimated using the previously described crystal structure of the Norwalk virus capsid (26), are indicated. The majority of amino acid sequence changes between the new strain and its previous closest relative occurred in the outer P2 subdomain of the capsid and are highlighted in boxes.

Tables

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TABLE 1.

Locations, dates, samples, and sequences obtained from norovirus outbreaks

Outbreak location	Start date^a	End date^a	Duration (days)	No. symptomatic^b	No. of positive samples (RNA Pol^c RT-PCR)	RNA Pol sequence variant	No. of 3′-terminal sequences (3,255 nt)	No. of genome sequences (7,558 nt)
Hosp^e A, ward 7E	9/25/02	10/2/02	7	20	1/1	1	1
Hosp A, ward 7B	10/7/02	10/14/02	8	14	2/4	1	1
Hosp A, ward 7A	10/7/02	10/10/02	4	14	1/2	1
Hosp A, ward 7A	10/25/02	10/30/02	6	22	5/7	1
Hosp A, ward 7D	10/26/02	11/4/02	10	15	3/5	2	2
Hosp A, ward 7C	10/26/02	11/4/02	10	25	11/15	1	10	2
Hosp A, ward 7F	11/20/02	11/25/02	6	17	5/6	3	4
Hosp A, ward 7C	11/22/02	12/27/02	6	13	2/5	1	2
Hosp A, ward 7E	11/22/02	12/4/02	13	22	3/10	1	3
Hosp A, ward 7D	11/22/02	11/29/02	8	11	3/6	1	1
Hosp A, ward 7A	11/28/02	12/3/02	6	14	1/1	1	1
Hosp A, ward 6A	12/13/02	12/16/02	3	18	6/8	4	2
Hosp A, ward 3A	1/20/03	1/27/03	7	25	1/1	1	1
Hosp A, ward 2A	1/20/03	1/29/03	9	26	5/9	1	4
Hosp A, ward 5E	2/17/03	2/21/03	5	9	7^d/10	1	7^d	1
Hosp B, ward L	9/29/02	10/5/02	7	25	8/8	1	6	6
Hosp B, ward E	10/7/02	10/10/02	4	14	1/3	1
Hosp E	12/21/02	1/10/03	20	30	2	1
Hosp C	2/13/03	2/26/03	13	48	3	1	1
Hosp D	3/24/03	4/2/03	9	16	3	1	1
Hosp F	4/7/03	4/15/03	8	12	1	1	1
Hosp G	5/16/03	5/22/03	7	19	4	5	1
Total					75/130		49

↵a Month/day/year.
↵b Number symptomatic includes patients, staff and relatives. Start and end dates refer to the dates restrictions on patient and staff movements were imposed by hospital infection control.
↵c Pol, polymerase.
↵d Three isolates from one immunocompromised patient.
↵e Hosp, hospital.

TABLE 2.
Mutations accumulated in virus genome in six patients infected during an outbreak
Sample no. Sample date^a Mutation at position (within 7,558-nt genome)^b:
1015 1761 3938 6503 6564 6736
B4S2 9/25/02 G T C T T A
B4S5 9/27/02 G T C T T A
B4S6 9/27/02 G T C T T A
B4S4 10/1/02 G T T C T G
B4S7 10/1/02 G C T C T G
B4S1 10/3/02 T C T C A G
↵a Month/day/year.
↵b Accumulated mutations are indicated by boldface type.