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Virology

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

Kate E. Dingle, ; Norovirus Infection Control in Oxfordshire Communities Hospitals
Kate E. Dingle
1Nuffield Department of Clinical Sciences, Oxford University
2Department of Microbiology, Oxford Radcliffe NHS Trust, John Radcliffe Hospital, Oxford, United Kingdom
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  • For correspondence: kate.dingle@ndcls.ox.ac.uk
DOI: 10.1128/JCM.42.9.3950-3957.2004
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  • FIG. 1.
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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.

  • FIG. 2.
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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.

  • FIG. 3.
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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 .

  • FIG. 4.
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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 locationStart dateaEnd dateaDuration (days)No. symptomaticbNo. of positive samples (RNA Polc RT-PCR)RNA Pol sequence variantNo. of 3′-terminal sequences (3,255 nt)No. of genome sequences (7,558 nt)
    Hospe A, ward 7E9/25/0210/2/027201/111
    Hosp A, ward 7B10/7/0210/14/028142/411
    Hosp A, ward 7A10/7/0210/10/024141/21
    Hosp A, ward 7A10/25/0210/30/026225/71
    Hosp A, ward 7D10/26/0211/4/0210153/522
    Hosp A, ward 7C10/26/0211/4/02102511/151102
    Hosp A, ward 7F11/20/0211/25/026175/634
    Hosp A, ward 7C11/22/0212/27/026132/512
    Hosp A, ward 7E11/22/0212/4/0213223/1013
    Hosp A, ward 7D11/22/0211/29/028113/611
    Hosp A, ward 7A11/28/0212/3/026141/111
    Hosp A, ward 6A12/13/0212/16/023186/842
    Hosp A, ward 3A1/20/031/27/037251/111
    Hosp A, ward 2A1/20/031/29/039265/914
    Hosp A, ward 5E2/17/032/21/03597d/1017d1
    Hosp B, ward L9/29/0210/5/027258/8166
    Hosp B, ward E10/7/0210/10/024141/31
    Hosp E12/21/021/10/03203021
    Hosp C2/13/032/26/031348311
    Hosp D3/24/034/2/03916311
    Hosp F4/7/034/15/03812111
    Hosp G5/16/035/22/03719451
    Total75/13049
    • ↵ 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 dateaMutation at position (within 7,558-nt genome)b:
    101517613938650365646736
    B4S29/25/02GTCTTA
    B4S59/27/02GTCTTA
    B4S69/27/02GTCTTA
    B4S410/1/02GT T C T G
    B4S710/1/02G C T C T G
    B4S110/3/02 T C T C A G
    • ↵ a Month/day/year.

    • ↵ b Accumulated mutations are indicated by boldface type.

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Mutation in a Lordsdale Norovirus Epidemic Strain as a Potential Indicator of Transmission Routes
Kate E. Dingle Norovirus Infection Control in Oxfordshire Communities Hospitals
Journal of Clinical Microbiology Sep 2004, 42 (9) 3950-3957; DOI: 10.1128/JCM.42.9.3950-3957.2004

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Mutation in a Lordsdale Norovirus Epidemic Strain as a Potential Indicator of Transmission Routes
Kate E. Dingle Norovirus Infection Control in Oxfordshire Communities Hospitals
Journal of Clinical Microbiology Sep 2004, 42 (9) 3950-3957; DOI: 10.1128/JCM.42.9.3950-3957.2004
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KEYWORDS

Caliciviridae Infections
mutation
norovirus

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