Regions of conservation and divergence in the 3′ untranslated sequences of genomic RNA from Ross River virus isolates

Faragher, S.G.; Dalgarno, L.

doi:10.1016/0022-2836(86)90287-1

Cited by 24 publications

(11 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The 39 UTRs of isolates T48 (mosquito), 2975B, 2982B, 3078B (birds) and QML1 (human) each contained the four-repeat nucleotide sequences described previously (Faragher & Dalgarno, 1986). Both isolates from wallabies (8961W and 9057W) had a 35 nt deletion after nt 54 of the 39 UTR that removed the first 22 nt from repeat sequence III, and which has been described previously (Faragher & Dalgarno, 1986). In addition, there were single (T48, 2982) and double (QML1) nucleotide deletions in the same region (211 and 211, 212, respectively) of the 23 nt putative promoter for negative-strand RNA synthesis (Kuhn et al, 1990), which immediately precedes the poly(A) tail of the genome.…”

Section: Resultsmentioning

confidence: 68%

Section: Resultsmentioning

confidence: 68%

See 1 more Smart Citation

Molecular evolutionary dynamics of Ross River virus and implications for vaccine efficacy

Jones

Lowry

Aaskov

et al. 2009

Journal of General Virology

View full text Add to dashboard Cite

Ross River virus (RRV) is a mosquito-borne member of the genus Alphavirus that causes epidemic polyarthritis in humans, costing the Australian health system at least US$10 million annually. Recent progress in RRV vaccine development requires accurate assessment of RRV genetic diversity and evolution, particularly as they may affect the utility of future vaccination. In this study, we provide novel RRV genome sequences and investigate the evolutionary dynamics of RRV from timestructured E2 gene datasets. Our analysis indicates that, although RRV evolves at a similar rate to other alphaviruses (mean evolutionary rate of approx. 8¾10"4 nucleotide substitutions per site year "1 ), the relative genetic diversity of RRV has been continuously low through time, possibly as a result of purifying selection imposed by replication in a wide range of natural host and vector species. Together, these findings suggest that vaccination against RRV is unlikely to result in the rapid antigenic evolution that could compromise the future efficacy of current RRV vaccines. INTRODUCTIONRoss River virus (RRV) is an alphavirus that infects a wide range of vertebrate hosts, including marsupials, equids, rodents, birds and fruit bats, and has multiple mosquito vectors, including several Aedes species (reviewed by Russell, 2002). Of the natural hosts, only humans and horses are known to develop symptoms (Doherty et al., 1963(Doherty et al., , 1972Azuolas et al., 2003). The disease in humans is known as epidemic polyarthritis (EPA) (Shope & Anderson, 1960) and is characterized by polyarthralgia in the small joints, principally of the hands and feet, as well as fever, rash and a range of other non-specific signs and symptoms. Patients may be incapacitated for several weeks after infection, but symptoms diminish in severity in the ensuing 30-40 weeks, leading to a full recovery. Up to approximately 7800 cases are reported annually from Australia (Australian Department of Health and Ageing, 2009) and an epidemic of RRV infection in the Pacific in 1979 and 1980 resulted in tens of thousands of clinical infections (Aaskov et al., 1981;Rosen et al., 1981; Tesh et al., 1981). Importantly, the Pacific epidemic of 1979-1980 suggests strongly that RRV is not dependent on purely sylvatic transmission cycles, and that urban transmission cycles are both possible and expected.Recently, there has been considerable interest in developing a vaccine against RRV infection (Yu & Aaskov, 1994;Aaskov et al., 1997;Kistner et al., 2007) as there is no cure for EPA, because RRV infections appear to confer lifelong immunity against a second clinical infection (Fraser, 1986) and because EPA has been estimated to cost the Australian health system more than US$10 million annually in direct medical costs (Aaskov et al., 1998), with millions more spent on mosquito control. Effective vaccination, whether by live-attenuated virus or inactivated virus, such as the formaldehyde-inactivated virus vaccine currently in development (Kistner et al., 2007), requires that circulat...

show abstract

Section: Resultsmentioning

confidence: 68%

Section: Resultsmentioning

confidence: 68%

Molecular evolutionary dynamics of Ross River virus and implications for vaccine efficacy

Jones

Lowry

Aaskov

et al. 2009

Journal of General Virology

View full text Add to dashboard Cite

show abstract

“…Alignment of the DC5692 and T48 genome sequences revealed a number of differences in the 3′ UTRs of these two viruses. Extensive variability in 3′ UTRs among RRV isolates has been previously reported (Faragher and Dalgarno, 1986), however, whether these differences impact the development of disease is not known. To test whether the differences in the 3′ UTRs contributed to pathogenesis in the mouse model, we generated a chimeric virus that encodes the DC5692 3′ UTR in the T48 strain genetic backbone (RR67).…”

Section: Discussionmentioning

confidence: 99%

Mutations in nsP1 and PE2 are critical determinants of Ross River virus-induced musculoskeletal inflammatory disease in a mouse model

et al. 2011

View full text Add to dashboard Cite

The viral determinants of Alphavirus-induced rheumatic disease have not been elucidated. We identified an RRV strain (DC5692) which, in contrast to the T48 strain, does not induce musculoskeletal inflammation in a mouse model of RRV disease. Substitution of the RRV T48 strain nonstructural protein 1 (nsP1) coding sequence with that from strain DC5692 generated a virus that was attenuated in vivo despite similar viral loads in tissues. In contrast, substitution of the T48 PE2 coding region with the PE2 coding region from DC5692 resulted in attenuation in vivo and reduced viral loads in tissues. In gain of virulence experiments, substitution of the DC5692 strain nsP1 and PE2 coding regions with those from the T48 strain was sufficient to restore full virulence to the DC5692 strain. These findings indicate that determinants in both nsP1 and PE2 have critical and distinct roles in the pathogenesis of RRV-induced musculoskeletal inflammatory disease in mice.

show abstract

“…Multiple alignments showed that the S_Korea isolate does not possess the 92 nt sequence from 11341-11433 in the virus genome and there was a low level of identity (92.19-93.75%) between S_Korea and other GETV strain at the 3'-UTR sequences. Despite possessing 3'-UTR sequences of different lengths, GETV isolates contain various numbers of an identical sequence element that could have originated from a large ancestral 3'-UTR [26,27].…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel Getah virus by Virus-Discovery-cDNA random amplified polymorphic DNA (RAPD)

Hu¹,

Zheng²,

Zhang

et al. 2012

BMC Microbiol

View full text Add to dashboard Cite

BackgroundThe identification of new virus strains is important for the study of infectious disease, but current (or existing) molecular biology methods are limited since the target sequence must be known to design genome-specific PCR primers. Thus, we developed a new method for the discovery of unknown viruses based on the cDNA - random amplified polymorphic DNA (cDNA-RAPD) technique. Getah virus, belonging to the family Togaviridae in the genus Alphavirus, is a mosquito-borne enveloped RNA virus that was identified using the Virus-Discovery-cDNA RAPD (VIDISCR) method.ResultsA novel Getah virus was identified by VIDISCR from suckling mice exposed to mosquitoes (Aedes albopictus) collected in Yunnan Province, China. The non-structural protein gene, nsP3, the structural protein gene, the capsid protein gene, and the 3'-untranslated region (UTR) of the novel Getah virus isolate were cloned and sequenced. Nucleotide sequence identities of each gene were determined to be 97.1–99.3%, 94.9–99.4%, and 93.6–99.9%, respectively, when compared with the genomes of 10 other representative strains of Getah virus.ConclusionsThe VIDISCR method was able to identify known virus isolates and a novel isolate of Getah virus from infected mice. Phylogenetic analysis indicated that the YN08 isolate was more closely related to the Hebei HB0234 strain than the YN0540 strain, and more genetically distinct from the MM2021 Malaysia primitive strain.

show abstract

Regions of conservation and divergence in the 3′ untranslated sequences of genomic RNA from Ross River virus isolates

Cited by 24 publications

References 19 publications

Molecular evolutionary dynamics of Ross River virus and implications for vaccine efficacy

Molecular evolutionary dynamics of Ross River virus and implications for vaccine efficacy

Mutations in nsP1 and PE2 are critical determinants of Ross River virus-induced musculoskeletal inflammatory disease in a mouse model

Identification of a novel Getah virus by Virus-Discovery-cDNA random amplified polymorphic DNA (RAPD)

Contact Info

Product

Resources

About