Absolute Linkage of Virulence and Central Nervous System Cell Tropism of Reoviruses to Viral Hemagglutinin

Weiner, Howard L.; Powers, M. Linda; Fields, Bernard N.

doi:10.1093/infdis/141.5.609

Cited by 210 publications

(179 citation statements)

References 19 publications

Supporting

Mentioning

175

Contrasting

Order By: Relevance

“…The report that clinical HSV-1 isolates are probably very mutable, at any rate in the TK gene (Parris & Harrington, 1982), suggests that mutation of genotypes in vivo prior to or following reactivation could account for the emergence of a more virulent virus in the infected individual (Kaerner et al, 1983). Clinical isolates of other encephalitic viruses with differing virulence are well known (Trent et al, 1981 ;Shapshak et al, 1982;Harvey & Volkman, 1983 ;Weiner et al, 1980). Herpetic infections leading to encephalitis are usually sporadic (Hammer et al, 1980) which would be in keeping with a rare virulence constellation of sites having arisen (by mutation or recombination) in an intrinsically less virulent virus.…”

Section: Discussionmentioning

confidence: 99%

Variable Restriction Endonuclease Sites of Herpes Simplex Virus Type 1 Isolates from Encephalitic, Facial and Genital Lesions and Ganglia

Chaney¹,

Warren

Subak‐Sharpe³

1983

Journal of General Virology

View full text Add to dashboard Cite

SUMMARYThe distribution of restriction endonuclease (RE) sites was compared for 84 herpes simplex virus type 1 (HSV-1) isolates obtained from the ganglia, facial lesions, genital lesions and from brain tissue from herpes encephalitis cases. The isolates came from Canada, the U.K., the U.S.A. and Japan. Out of a total of 224 sites identified, 87 were variable. Three of the 30 most variable sites were at significantly (P < 0-05) different frequencies in groups of isolates from distinct anatomical sites of isolation; one of these, and a further two sites, were at significantly different frequencies in groups from distinct geographical origins. There are at least two inter-related linkage groups. However, most of the site combinations appear to be random. The variability of RE sites in contiguous genome segments, which include both non-coding and coding sequences, show a marked heterogeneity, indicating that some viral gene sequences are more variable than others. The three RE sites at different frequencies in viral groups from distinct anatomical sites of isolation are in two genome segments : map units 27 to 35 and 50 to 57. We infer from the observed associations with anatomical site of viral isolation that part of at least one of these segments may modulate viral virulence in man following infection.

show abstract

Section: Discussionmentioning

confidence: 99%

Variable Restriction Endonuclease Sites of Herpes Simplex Virus Type 1 Isolates from Encephalitic, Facial and Genital Lesions and Ganglia

Chaney¹,

Warren

Subak‐Sharpe³

1983

Journal of General Virology

View full text Add to dashboard Cite

show abstract

“…While attachment protein 1 is a major determinant of reovirus pathogenesis (5,30,44,45,67), nonstructural protein 1s also is required for production of maximal viral titers in the gastrointestinal tract (4) and for hematogenous spread after peroral (4) or intramuscular (28) inoculation. Consistent with a role for 1s in viral replication at mucosal sites, our results demonstrate that the T3D C 1s protein enhances viral replication in the respiratory tract and hematogenous dissemination ( Fig.…”

Section: Fig 8 Construction and Characterization Of Rst3dmentioning

confidence: 99%

Genetic Determinants of Reovirus Pathogenesis in a Murine Model of Respiratory Infection

Nygaard

Lahti

Ikizler

et al. 2013

J Virol

View full text Add to dashboard Cite

Many viruses invade mucosal surfaces to establish infection in the host. Some viruses are restricted to mucosal surfaces, whereas others disseminate to sites of secondary replication. Studies of strain-specific differences in reovirus mucosal infection and systemic dissemination have enhanced an understanding of viral determinants and molecular mechanisms that regulate viral pathogenesis. After peroral inoculation, reovirus strain type 1 Lang replicates to high titers in the intestine and spreads systemically, whereas strain type 3 Dearing (T3D) does not. These differences segregate with the viral S1 gene segment, which encodes attachment protein 1 and nonstructural protein 1s. In this study, we define genetic determinants that regulate reovirus-induced pathology following intranasal inoculation and respiratory infection. We report that two laboratory isolates of T3D, T3D C and T3D F , differ in the capacity to replicate in the respiratory tract and spread systemically; the T3D C isolate replicates to higher titers in the lungs and disseminates, while T3D F does not. Two nucleotide polymorphisms in the S1 gene influence these differences, and both S1 gene products are involved. T3D C amino acid polymorphisms in the tail and head domains of 1 protein influence the sensitivity of virions to protease-mediated loss of infectivity. The T3D C polymorphism at nucleotide 77, which leads to coding changes in both S1 gene products, promotes systemic dissemination from the respiratory tract. A 1s-null virus produces lower titers in the lung after intranasal inoculation and disseminates less efficiently to sites of secondary replication. These findings provide new insights into mechanisms underlying reovirus replication in the respiratory tract and systemic spread from the lung. Many viruses enter host organisms by invading mucosal surfaces, including those that line the respiratory tract. Infection by some pneumotropic viruses is restricted to the respiratory tract, whereas others replicate in the lung and disseminate to sites of secondary replication. Mammalian orthoreoviruses (reoviruses) naturally infect both the respiratory and gastrointestinal tracts (1). Reovirus strains differ in the capacity to replicate at mucosal sites and disseminate systemically. Studies of strain-specific differences in reovirus mucosal infection and systemic spread have enhanced an understanding of viral determinants and molecular mechanisms that regulate reovirus pathogenesis. For example, after peroral or intratracheal inoculation, reovirus strain type 1 Lang (T1L) replicates to higher titers than does strain type 3 Dearing (T3D) (2). This difference in replication efficiency at the site of primary replication segregates with the reovirus S1 gene segment (2, 3). Like T1L, reassortant virus 3HA1, with nine gene segments from T3D and an S1 gene from T1L, replicates to high titers in mucosal tissues (2). In contrast, reassortant virus 1HA3, with nine gene segments from T1L and an S1 gene from T3D, fails to replicate to high titers at those sit...

show abstract

“…32 It is this interaction that allows reovirus to infect the host presumably via the protein 1-M cell interaction. 30,31 M cells facilitate antigen sampling allowing uptake by antigen presenting cells located proximal to M cells in the mucosal inductive tissues such as Peyer's patch.…”

Section: Discussionmentioning

confidence: 99%

Gene transfer facilitated by a cellular targeting molecule, reovirus protein σ1

Boysun

Csencsits

et al. 2000

Gene Ther

View full text Add to dashboard Cite

To facilitate eventual genetic vaccination of mucosal tissues, a receptor-mediated gene transfer system was devised using the reovirus adhesin, protein 1. Highly efficient uptake and internalization of protein 1 polylysine (PL) DNA complexes could be demonstrated by fluorescent microscopy. Successful cellular transfection of rodent and human cell lines was obtained with the recombinant protein 1 as a PL-DNA complex, and could be shown to be receptor-specific. Transfection efficiency was dependent upon the

show abstract

Absolute Linkage of Virulence and Central Nervous System Cell Tropism of Reoviruses to Viral Hemagglutinin

Cited by 210 publications

References 19 publications

Variable Restriction Endonuclease Sites of Herpes Simplex Virus Type 1 Isolates from Encephalitic, Facial and Genital Lesions and Ganglia

Variable Restriction Endonuclease Sites of Herpes Simplex Virus Type 1 Isolates from Encephalitic, Facial and Genital Lesions and Ganglia

Genetic Determinants of Reovirus Pathogenesis in a Murine Model of Respiratory Infection

Gene transfer facilitated by a cellular targeting molecule, reovirus protein σ1

Contact Info

Product

Resources

About