Isolation of semliki forest virus from Aedes (Aedimorphus) argenteopunctatus (theobald) collected in Portuguese East Africa

McIntosh, B. M.; Worth, C. Brooke; Kokernot, R. H.

doi:10.1016/0035-9203(61)90025-6

Cited by 34 publications

(29 citation statements)

References 9 publications

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“…The SFV prototype was isolated in 1942 from a pool of mosquitoes in Uganda (40). The A7(74) strain (4) is a derivative of an SFV strain isolated from mosquitoes in Mozambique in 1959 (26). Several strains of SFV, such as L10 (4) and SFV4 (24), cause lethal encephalitis in mice of all ages, leading to death of the animals in a few days (3,11), whereas A7(74) infection of adult mice is asymptomatic per se but leads to axonal demyelination mediated by CD8 ϩ T cells (2).…”

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confidence: 99%

Replicase Complex Genes of Semliki Forest Virus Confer Lethal Neurovirulence

Tuittila

Santagati²,

Röyttä

et al. 2000

J Virol

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Semliki Forest virus (SFV) is a mosquito-transmitted pathogen of small rodents, and infection of adult mice with SFV4, a neurovirulent strain of SFV, leads to lethal encephalitis in a few days, whereas mice infected with the avirulent A7(74) strain remain asymptomatic. In adult neurons, A7(74) is unable to form virions and hence does not reach a critical threshold of neuronal damage. To elucidate the molecular mechanisms of neurovirulence, we have cloned and sequenced the entire 11,758-nucleotide genome of A7(74) and compared it to the highly neurovirulent SFV4 virus. We found several sequence differences and sought to localize determinants conferring the neuropathogenicity by using a panel of chimeras between SFV4 and a cloned recombinant, rA774. We first localized virulence determinants in the nonstructural region by showing that rA774 structural genes combined with the SFV4 nonstructural genome produced a highly virulent virus, while a reciprocal recombinant was asymptomatic. In addition to several amino acid mutations in the nonstructural region, the nsp3 gene of rA774 displayed an opal termination codon and an in-frame 21-nucleotide deletion close to the nsp4 junction. Replacement in rA774 of the entire nsp3 gene with that of SFV4 reconstituted the virulent phenotype, whereas an arginine at the opal position significantly increased virulence, leading to clinical symptoms in mice. Completion of the nsp3 deletion in rA774 did not increase virulence. We conclude that the opal codon and amino acid mutations other than the deleted residues are mainly responsible for the attenuation of A7(74) and that the attenuating determinants reside entirely in the nonstructural region.Semliki Forest virus (SFV) is an enveloped positive-stranded RNA virus of the family Togaviridae. The SFV prototype was isolated in 1942 from a pool of mosquitoes in Uganda (40). The A7(74) strain (4) is a derivative of an SFV strain isolated from mosquitoes in Mozambique in 1959 (26). Several strains of SFV, such as L10 (4) and SFV4 (24), cause lethal encephalitis in mice of all ages, leading to death of the animals in a few days (3, 11), whereas A7(74) infection of adult mice is asymptomatic per se but leads to axonal demyelination mediated by CD8 ϩ T cells (2). However, the severity of A7(74) infection is strictly age dependent, being lethal for neonatal mice less than 2 weeks old (8, 27), probably because the strain is capable of virion formation in propagating neurons, unlike in mature neurons (27).SFV nonstructural proteins (nsP) are translated as a polyprotein (nsP1234) from the genomic 42S RNA, and they form essential components of viral RNA replication and transcription complexes (14). The nsP1 protein is a methyl-and guanylyltransferase (1, 18), whereas the nsP2 is a proteinase (45) and nucleoside triphosphatase (33). The nsp3 gene product is a phosphoprotein, and it has been proposed to function together with nsP1 in anchoring the replication complex proteins to cytoplasmic membrane structures (30, 31). In Sindbis virus (SIN), p123 a...

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confidence: 99%

Replicase Complex Genes of Semliki Forest Virus Confer Lethal Neurovirulence

Tuittila

Santagati²,

Röyttä

et al. 2000

J Virol

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“…neurons in the CNS (Smithburn & Haddow, 1944). Strains such as A7 (McIntosh et al, 1961) or M9 are avirulent but induce demyelination by a mechanism that involves the infection of oligodendrocytes (Atkins, 1983 ;Atkins et al, 1990;Sheahan et al, 1983;Gates et al, 1984Gates et al, , 1985Fazakerley & Webb, 1987;Smyth et al, 1990;Balluz et al, 1993). A7 is also lethal for developing fetuses (Atkins et aI., 1982) and mutants derived from it, such as ts22, are teratogenic (Hearne et al, 1987).…”

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confidence: 99%

“…Although SFV4-(mut 8902 a/g) has some of the characteristics of A7, there must be other attenuating mutations or sequences in the A7 genome, since SFV4-(mut 8902 a/g) also retains some of the virulence of SFV4. The A7 strain of SFV is in fact an independent avirutent isolate (McIntosh et at., 1961). Furthermore, there is a divergent sequence present in the A7 3' noncoding region compared to SFV4.…”

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A single amino acid change in the E2 spike protein of a virulent strain of Semliki Forest virus attenuates pathogenicity

Glasgow

Killen

Liljeström

et al. 1994

Journal of General Virology

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The virulent strain SFV4 of Semliki Forest virus (SFV), produced from the infectious clone pSP6-SFV4, is lethal after intranasal (i.n.) infection of adult mice and for pregnant mice after intraperitoneal (i.p.) infection. In contrast, the A7 strain of SFV is avirulent when given i.n. to adult mice, but induces fetal death in pregnant mice after i.p. infection. The nucleotide and deduced amino acid sequences of part of the core and all of the envelope region of A7-SFV were determined and compared to those of SFV4. A7 differed from SFV4 at 80 nucleotides (nt) in the coding sequence, 15 of which were associated with amino acid differences and seven of which (two in the E2 protein and five in El) were nonconservative. The 3' non-coding sequence of A7 was longer (415 nt) than that of SFV4 (263 nt) and a divergent sequence of 181 nt was present adjacent to the end of the E1 coding region. The effects on virulence of two mutations in the E2 gene of SFV4, resulting in the non-conservative amino acid substitutions present in A7, were analysed. One mutation (mut 8729 a/c) resulted in only slight attenuation, whereas the other (mut 8902 a/g) resulted in avirulence for pregnant mice. However, mut 8902 a/g was lethal for the majority of developing fetuses after i.p. infection of the mother.

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“…The SFV virulent strain L10 (WT) causes lethal encephalitis in small rodents but infection with the avirulent A774 (A7) variant strain is asymptomatic. The L10 strain is a derivative of SFV isolated from a pool of mosquitoes (Aedes abnormalis) in Uganda in 1942 (Smithburn & Haddow, 1944) and A7 originates from mosquitoes (,4. argenteopunctatus) caught in Mozambique in 1959(McIntosh et al, 1961. The A7 strain was established from the original isolate (AR2066) by Bradish et al (1971).…”

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Multiple repeating motifs are found in the 3'-terminal non-translated region of Semliki Forest virus A7 variant genome

Santagati

Itäranta

Koskimies

et al. 1994

Journal of General Virology

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We have analysed the cDNA coding for the envelope glycoprotein (El) gene and the terminal non-translated regions (NTRs) of the avirulent Semliki Forest virus (SFV) A774 (A7) variant. The E1 gene exhibited 98-5 % identity to the SFV prototype strain L10 (WT) sequence at the nucleotide level. Of the 34 single base substitutions, six led to a change in the deduced amino acid sequence. The 3' NTR of A7 consisted of a I01 nucleotide sequence, not found in WT, followed by five tandemly arranged sequence motifs, two of which were truncated forms of the others. One full-length and one truncated repeat are found at the 3' NTR of WT, The repeats of A7 were followed by a non-repeating sequence, very similar to the equivalent region in WT. Owing to the unique sequence motif and the tandem repeats, the 3' NTR of A7 is 334 nucleotides longer than that of WT. Each of the repeats had an internal 12 nucleotide motif complementary to a conserved sequence in the 5'-terminal non-structural protein 1-encoding region, thought to be important in alphavirus RNA replication, In the 5' NTR, three point mutations were found. The conserved sequence binding to the repeated 3 / motifs was identical in A7 and WT.

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Isolation of semliki forest virus from Aedes (Aedimorphus) argenteopunctatus (theobald) collected in Portuguese East Africa

Cited by 34 publications

References 9 publications

Replicase Complex Genes of Semliki Forest Virus Confer Lethal Neurovirulence

Replicase Complex Genes of Semliki Forest Virus Confer Lethal Neurovirulence

A single amino acid change in the E2 spike protein of a virulent strain of Semliki Forest virus attenuates pathogenicity

Multiple repeating motifs are found in the 3'-terminal non-translated region of Semliki Forest virus A7 variant genome

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