The extent of homologous recombination in members of the genus Flavivirus

Twiddy, S. Susanna; Holmes, Edward C.

doi:10.1099/vir.0.18660-0

Cited by 132 publications

(120 citation statements)

References 42 publications

(40 reference statements)

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“…Consequently, three distinct lineages of SLEV have been reported in Brazil, suggesting that the virus is circulating and dispersing throughout the Americas. This hypothesis is supported by a recent finding of Twiddy and Holmes (2003) who demonstrated strain GMO94, isolated in Guatemala, to be a recombinant of South (CorAn 9124, Cordoba, Argentina) and North (TNM-711K, Tennessee, US) American strains.…”

Section: Discussionsupporting

confidence: 70%

Genetic characterization of St. Louis encephalitis virus isolated from human in São Paulo, Brazil

Santos

Sallum

Franco

et al. 2006

Mem. Inst. Oswaldo Cruz

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(Calisher et al. 1989). The genome of flaviviruses contains a single-stranded positive sense RNA, about 10,800 nucleotides long that encodes 10 distinct proteins in a single reading frame (Chambers et al. 1990). SLEV is the etiologic agent of St. Louis encephalitis, a disease of epidemiological importance in North America. This virus was first isolated in the United States of America (US) in 1933, during an outbreak, which occurred in St. Louis and Kansas City, Mo. (Muckenfuss et al. 1934). In the US intermittent and unpredictable epidemics have been occurring during the last decades. The majority of SLEV infections is sub clinical or result in mild illness. The severity of infections is strongly dependent on the age of a patient, and the case fatality rate during epidemics ranges from 2% in young adults to more than 22% in the elders (Monath & Heinz 1996). In spite of being endemic in Central and South America, causing sporadic illness, occurrence of SLEV outbreaks is unknown (Spence 1980, Monath & Heinz 1996.The biological cycle of SLEV in nature involves primarily wild birds and several mosquito species; humans and other mammals are considered to be incidental hosts (Monath & Heinz 1996). In the US, Culicinae mosquitoes and birds, Passeriformes and Columbiformes, are involved in the dynamics of SLEV transmission. The transmission Financial support: Fapesp (no. 2004/07819-6) and CNPq (no. 305339/2003-6) cycle varies regionally, depending on the biology of mosquito species, virulence of SLEV strains and susceptibility to infection of vertebrate hosts (Monath & Tsai 1987, Day 2001, Reisen 2003. In Central and South America SLEV transmission cycle is not well defined, but it may include mosquito species of the genera Culex, Mansonia, Haemagogus, and Sabethes. A variety of bird taxa, including herons, egrets, and cormorant may be virus reservoirs (Spence 1980, Monath & Heinz 1996, Reisen 2003.The occurrence of SLEV in Brazil was recorded in 1953, by the finding of antibodies to this virus in residents of the Amazon Valley (Causey & Theiller 1958). A pool of mosquito Sabethes belisarioi, captured along the Belém-Brasília highway, was the source for the first isolation of a SLEV strain (Causey et al. 1964). Later in 1970 and 1978 two strains were recovered from human blood in Amazon region. In both cases the patients developed a febrile illness with jaundice, neither of them presenting neurological involvement (Pinheiro et al. 1981, Vasconcelos et al. 1998. SLEV was also found in the Southeast region of Brazil where it was isolated from wild birds, rodents, and sentinel mice during a surveillance program on arbovirus activity carried out in the state of São Paulo from 1967 to 1969 (Lopes et al. 1979).In the summer of 2004, after more than two decades of the last human Brazilian report, a clinical case of infection by SLEV was detected in the state of São Paulo. Epidemiologic data about the SLEV case was fully detailed by Rocco et al. (2005). Briefly, a patient, suffering from severe uncharacterized febrile illnes...

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Section: Discussionsupporting

confidence: 70%

Genetic characterization of St. Louis encephalitis virus isolated from human in São Paulo, Brazil

Santos

Sallum

Franco

et al. 2006

Mem. Inst. Oswaldo Cruz

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“…However, an infectious HCV chimera comprising the complete open reading frame of a subtype 1b strain and the 59-and 39UTRs of a subtype 1a strain has been constructed and is infectious in vivo (Yagani et al, 1998). Recombination in other flaviviruses has now been demonstrated on a number of occasions (Becher et al, 2001;Worobey & Holmes, 2001;Twiddy & Holmes, 2003), and recently a natural intergenotypic recombinant (2k/1b) of HCV was identified in St Petersburg (Russia) (Kalinina et al, 2002). Our phylogenetic analyses based on two different genomic regions, 59UTR-core and NS5B, demonstrate the existence of natural intragenotypic HCV recombinant strains (1a/1b) circulating in the Peruvian population.…”

Section: Discussionmentioning

confidence: 89%

“…Tolou et al, 2001;Uzcategui et al, 2001;, hepaciviruses (GB virus C/hepatitis G virus) (Worobey & Holmes, 2001) and Japanese encephalitis or St Louis encephalitis virus (Twiddy & Holmes, 2003). There have been few reports on recombination between HCV strains of different genotypes (Kalinina et al, 2002;Yun et al, 1996) and it has been suggested that these events are rare in vivo and that the resultant recombinants are usually not viable (Simmonds et al, 1994;Smith & Simmonds, 1997).…”

Section: Introductionmentioning

confidence: 99%

Evidence of intratypic recombination in natural populations of hepatitis C virus

Colina

Casañe

Vásquez³

et al. 2004

Journal of General Virology

114

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Hepatitis C virus (HCV) has high genomic variability and, since its discovery, at least six different types and an increasing number of subtypes have been reported. Genotype 1 is the most prevalent genotype found in South America. In the present study, three different genomic regions (59UTR, core and NS5B) of four HCV strains isolated from Peruvian patients were sequenced in order to investigate the congruence of HCV genotyping for these three genomic regions. Phylogenetic analysis using 59UTR-core sequences found strain PE22 to be related to subtype 1b. However, the same analysis using the NS5B region found it to be related to subtype 1a. To test the possibility of genetic recombination, phylogenetic studies were carried out, revealing that a crossover event had taken place in the NS5B protein. We discuss the consequences of this observation on HCV genotype classification, laboratory diagnosis and treatment of HCV infection.

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“…This prediction is supported by data from sex chromosomes (Berlin and Ellegren 2006;Wykoff et al 2002), mitochondrial genomes (Nachman et al 1994(Nachman et al , 1996Rand and Kann 1996) and Drosophila genomic regions with different recombination rates (Haddrill et al 2007). There is evidence of homologous recombination in DNA viruses (Thiry et al 2004;Wilkinson and Weller 2003) and in both positive strand (Agol 2006;Lukashev 2005;Twiddy and Holmes 2003;Worobey and Holmes 1999) and negative-strand (Hughes 2007;Kukkonen et al 2005;Spann et al 2003) ssRNA viruses. Nonetheless, it seems probable that, because of their compact genomes, RNA viruses have considerably higher rates of recombination per nucleotide site than those of many DNA viruses, particularly dsDNA viruses, whose genomes are much larger.…”

Section: Discussionmentioning

confidence: 99%

More effective purifying selection on RNA viruses than in DNA viruses

Hughes

2007

Gene

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Analysis of the pattern of nucleotide diversity in 222 independent viral sequence datasets showed the prevalence of purifying selection. In spite of the higher mutation rate of RNA viruses, our analyses revealed stronger evidence of the action of purifying selection in RNA viruses than in DNA viruses. The ratio of nonsynonymous to synonymous nucleotide diversity was significantly lower in RNA viruses than in DNA viruses, indicating that nonsynonymous mutations have been removed at a greater rate (relative to the mutation rate) in the former than in the latter. Moreover, statistics that measure the occurrence of rare polymorphisms revealed significantly a greater excess of rare nonsynonymous polymorphisms in RNA viruses than in DNA viruses but no difference with respect to synonymous polymorphisms. Since rare nonsynonymous polymorphisms are likely to be undergoing the effects of purifying selection acting to eliminate them, this result implies a stronger signature of ongoing purifying selection in RNA viruses than in DNA viruses. Across datasets from both DNA viruses and RNA viruses, we found a negatively allometric relationship between nonsynonymous and synonymous nucleotide diversity; in other words, nonsynonymous nucleotide diversity increased with synonymous nucleotide diversity at a less than linear rate. These findings are most easily explained by the occurrence of slightly deleterious mutations. The fact that the negative allometry was more pronounced in RNA viruses than in DNA viruses provided additional evidence that purifying selection is more effective in the former than in the latter.

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The extent of homologous recombination in members of the genus Flavivirus

Cited by 132 publications

References 42 publications

Genetic characterization of St. Louis encephalitis virus isolated from human in São Paulo, Brazil

Genetic characterization of St. Louis encephalitis virus isolated from human in São Paulo, Brazil

Evidence of intratypic recombination in natural populations of hepatitis C virus

More effective purifying selection on RNA viruses than in DNA viruses

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