Norovirus Recombination in ORF1/ORF2 Overlap

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Abstract

Norovirus (NoV) genogroups I and II (GI and GII) are now recognized as the predominant worldwide cause of outbreaks of acute gastroenteritis in humans. Three recombinant NoV GII isolates were identified and characterized, 2 of which are unrelated to any previously published recombinant NoV. Using data from the current study, published sequences, database searches, and molecular techniques, we identified 23 recombinant NoV GII and 1 recombinant NoV GI isolates. Analysis of the genetic relationships among the recombinant NoV GII isolates identified 9 independent recombinant sequences; the other 14 strains were close relatives. Two of the 9 independent recombinant NoV were closely related to other recombinants only in the polymerase region, and in a similar fashion 1 recombinant NoV was closely related to another only in the capsid region. Breakpoint analysis of recombinant NoV showed that recombination occurred in the open reading frame (ORF)1/ORF2 overlap. We provide evidence to support the theory of the role of subgenomic RNA promoters as recombination hotspots and describe a simple mechanism of how recombination might occur in NoV.

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Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination.

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The development of an effective human immunodeficiency virus type 1 (HIV-1) vaccine is likely to depend on knowledge of circulating variants of genes other than the commonly sequenced gag and env genes. In addition, full-genome data are particularly limited for HIV-1 subtype C, currently the most commonly transmitted subtype in India and worldwide. Likewise, little is known about sequence variation of HIV-1 in India, the country facing the largest burden of HIV worldwide. Therefore, the objective of this study was to clone and characterize the complete genome of HIV-1 from seroconverters infected with subtype C variants in India. Cocultured HIV-1 isolates were obtained from six seroincident individuals from Pune, India, and virtually full-length HIV-1 genomes were amplified, cloned, and sequenced from each. Sequence analysis revealed that five of the six genomes were of subtype C, while one was a mosaic of subtypes A and C, with multiple breakpoints in env, nef, and the 3' long terminal repeat as determined by both maximal chi2 analysis and phylogenetic bootstrapping. Sequences were compared for preservation of known cytotoxic T lymphocyte (CTL) epitopes. Compared with those of the HIV-1LAI sequence, 38% of well-defined CTL epitopes were identical. The proportion of nonconservative substitutions for Env, at 61%, was higher (P < 0.001) than those for Gag (24%), Pol (18%), and Nef (32%). Therefore, characterized CTL epitopes demonstrated substantial differences from subtype B laboratory strains, which were most pronounced in Env. Because these clones were obtained from Indian seroconverters, they are likely to facilitate vaccine-related efforts in India by providing potential antigens for vaccine candidates as well as for assays of vaccine responsiveness.

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Some genes in prokaryotes consist of a mosaic of regions derived from different ancestors by horizontal gene transfer. A method is described for demonstrating the statistical significance of such mosaic structure and for locating the crossover points separating different regions.

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Author and article information

Journal

Journal ID (nlm-ta): Emerg Infect Dis

Journal ID (iso-abbrev): Emerging Infect. Dis

Journal ID (publisher-id): EID

Title: Emerging Infectious Diseases

Publisher: Centers for Disease Control and Prevention

ISSN (Print): 1080-6040

ISSN (Electronic): 1080-6059

Publication date (Print): July 2005

Volume: 11

Issue: 7

Pages: 1079-1085

Affiliations

[* ]University of New South Wales, Sydney, New South Wales, Australia;

[† ]University of Tokyo, Tokyo, Japan;

[‡ ]Prince of Wales Hospital, Randwick, New South Wales, Australia

Author notes

Address for correspondence: Peter A. White, School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales, Sydney 2052, New South Wales, Australia; fax: 61-9-385-1591; email: p.white@ 123456unsw.edu.au

Article

Publisher ID: 04-1273

DOI: 10.3201/eid1107.041273

PMC ID: 3371806

PubMed ID: 16022784

SO-VID: 2862c3c6-0273-4a1c-bd1a-8ba8d13f182e

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Norovirus Recombination in ORF1/ORF2 Overlap

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IEEE: COVID-19 related research

Most cited references 33

TreeView: an application to display phylogenetic trees on personal computers.

Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination.

Analyzing the mosaic structure of genes.

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