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

Abstract

An increase in norovirus outbreaks was reported internationally during 2002 and 2003 and was also observed in Oxfordshire (United Kingdom) hospitals. To understand their epidemiological relationships, viruses from 22 outbreaks (15 from one hospital) were subjected to nucleotide sequencing. The 3-terminal 3,255 nt or complete genomes were determined for 49 viruses. All outbreaks were caused by a genogroup II norovirus related to the Lordsdale virus (GII 4), common in healthcare settings. The norovirus mutation rate was sufficiently high that the 3,255-nucleotide sequences allowed separate and potentially connected outbreaks to be identified, since all outbreaks with identical sequences were temporally or geographically linked. The high mutation rate was further indicated by four mutations and three microheterogeneities in 3,255 nucleotides during 17 days of norovirus shedding by an immunocompromised patient. The data suggested that multiple virus introductions from the community, occasional transmission among wards, and one instance of ongoing environmental contamination had occurred. The accumulation, or lack, of mutations within an outbreak was also used to indicate the predominant transmission route. In an outbreak where person-to-person spread was thought to predominate, six mutations were detected throughout the genome, whereas one mutation was detected when point source infection was suspected. This norovirus epidemic strain differed from its closest previously described relative by 11.4 to 13.6% in the outer P2 domain of the capsid, which also had a single-amino-acid insertion. Alterations to the capsid structure compared to previous noroviruses may explain the increased number of outbreaks during 2002 and 2003.

Apparently non-specific results found using a norovirus antigen immunoassay for fecal specimens from neonates

“…10 Other reports showed a high molecular diversity and multiple mutations during outbreaks in the United Kingdom or Japan. 11,12 Obviously, as all test results were obtained with the same lot, we cannot exclude kit-specific false positive results.…”

Genetic Analysis of Noroviruses in Chiba Prefecture, Japan, between 1999 and 2004

“…Moreover, worldwide, the GII-4 genotype (Bristol virus-like genotype) has been shown to be the predominant strain of NV associated with gastroenteritis (13,21,(34)(35)(36). Changes in the phylogenetic and genetic characteristics of GII-4 genotype strains have also been reported (9,21).…”

“…They are one of the most common causes of gastroenteritis and have been detected in fecal samples from both humans (12,15,28) and animals (20,30,37). Human-associated NV outbreaks resulting from ingestion of contaminated water or food, such as oysters (4,5,18,23), and outbreaks in public places, particularly hospitals, schools, and cruise ships (9,11,22,36), pose an important public health problem.Reverse transcription-PCR (RT-PCR) and sequencing of the partial viral genome are the most popular and useful procedures for obtaining epidemiological and genetic information on NVs. Human NVs can be divided into two genogroups, genogroups GI and GII, by genetic analysis of the RNA polymerase and capsid regions (1, 15), with several genotype classifications having been reported independently (1,16,33).…”

“…They are one of the most common causes of gastroenteritis and have been detected in fecal samples from both humans (12,15,28) and animals (20,30,37). Human-associated NV outbreaks resulting from ingestion of contaminated water or food, such as oysters (4,5,18,23), and outbreaks in public places, particularly hospitals, schools, and cruise ships (9,11,22,36), pose an important public health problem.…”

Emerging GII.4 norovirus variants affect children with diarrhea in Palermo, Italy in 2006

“…As soon as surveillance and molecular epidemiological studies for NoV have been implemented, several GII.4 genetic variants have been identified [Fankhauser et al, 1998;Noel et al, 1999;Dingle, 2004;Lopman et al, 2004;Widdowson et al, 2004;Siebenga et al, 2007b]. Such variants are probably the result of a selection, driven by mechanisms of antigenic escape, from a pool of co-circulating strains [Green, 2007].…”