Replication of Ljungan virus in cell culture: The genomic 5′-end, infectious cDNA clones and host cell response to viral infections

Ekström, Jens‐Ola; Tolf, Conny; Fahlgren, Camilla; Johansson, E. Susanne; Arbrandt, Gustav; Niklasson, Bo; Edman, Kjell-A.; Lindberg, Anders

doi:10.1016/j.virusres.2007.06.004

Cited by 19 publications

(16 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Domains Ia to Ic (nt 1 to 124) located upstream of the pyrimidine-rich region has a relatively conserved primary structure with the predicted covariant mutations. Domains Ia to Ic are likely to form a large hairpin structure at the extreme 5= end of the genome (20), analogous to that found in other picornaviruses (33). The 3= end of the 5= UTR of DHAV shares high sequence identity with the PTV-1 IRES, implying that it is relatively easy to map certain features of the PTV-1 IRES onto the 3= end of the 5= UTR sequence of DHAV.…”

Section: Resultssupporting

confidence: 54%

Duck Hepatitis A Virus Possesses a Distinct Type IV Internal Ribosome Entry Site Element of Picornavirus

Pan

Yang

Zhou

et al. 2012

J Virol

View full text Add to dashboard Cite

Sequence analysis of duck hepatitis virus type 1 (DHV-1) led to its classification as the only member of a new genus, Avihepatovirus, of the family Picornaviridae, and so was renamed duck hepatitis A virus (DHAV). The 5= untranslated region (5= UTR) plays an important role in translation initiation and RNA synthesis of the picornavirus. Here, we provide evidence that the 651-nucleotide (nt)-long 5= UTR of DHAV genome contains an internal ribosome entry site (IRES) element that functions efficiently in vitro and within BHK cells. Comparative sequence analysis showed that the 3= part of the DHAV 5= UTR is similar to the porcine teschovirus 1 (PTV-1) IRES in sequence and predicted secondary structure. Further mutational analyses of the predicted domain IIId, domain IIIe, and pseudoknot structure at the 3= end of the DHAV IRES support our predicted secondary structure. However, unlike the case for the PTV-1 IRES element, analysis of various deletion mutants demonstrated that the optimally functional DHAV IRES element with a size of approximately 420 nt is larger than that of PTV-1 and contains other peripheral domains (Id and Ie) that do not exist within the type IV IRES elements. The domain Ie, however, could be removed without significant loss of activity. Surprisingly, like the hepatitis A virus (HAV) IRES element, the activity of DHAV IRES could be eliminated by expression of enterovirus 2A protease. These findings indicate that the DHAV IRES shares common features with type IV picornavirus IRES elements, whereas it exhibits significant differences from type IV IRESs. Therefore, we propose that DHAV possesses a distinct type IV IRES element of picornavirus.T he internal ribosome entry site (IRES) elements have the function to direct cap-independent internal initiation of protein synthesis, which is mechanistically quite different from the canonical cap-dependent mechanism for the translation initiation of the majority of cellular mRNAs (3). Earlier studies have indicated that all cytoplasmic cellular mRNAs possess a 5= terminal cap structure (m7GpppG. . .) that is recognized by the translation initiation factor complex-eukaryotic initiation factor 4 (eIF4F), which contains three proteins including eIF4E (cap-binding protein); eIF4A (ATP-dependent RNA helicase); and eIF4G, which acts as a protein scaffold. This complex of proteins acts as a bridge between the mRNA and the 40S ribosomal subunit via its interaction with eIF3 by multiple protein-protein interactions (23). In contrast to the cellular mRNAs, no cap structure exists at the 5= terminus of some viral mRNAs, such as those of picornaviruses and relevant viruses like hepatitis C virus (HCV). Initiation of protein synthesis for these viruses which rely on cap structure is termed internal initiation; in this case, the IRES element located within the 5= untranslated region (5= UTR) of the viral genome can exert the function to direct translation initiation (4, 19). Previous studies have showed that these IRES elements contain diverse secondary structures with ...

show abstract

Section: Resultssupporting

confidence: 54%

Duck Hepatitis A Virus Possesses a Distinct Type IV Internal Ribosome Entry Site Element of Picornavirus

Pan

Yang

Zhou

et al. 2012

J Virol

View full text Add to dashboard Cite

show abstract

“…This study also showed, together with the single-step growth curve and the observed onset of CPE, that there is a lag phase between the initial phase of viral replication and the CPE. The same phenomenon has previously been observed for another picornavirus, the Ljungan virus of the Parechovirus genus (28,80). Possibly, this delay of CPE is a consequence of a virus that is not yet completely adapted to its host cell.…”

Section: Discussionsupporting

confidence: 80%

A Single Coxsackievirus B2 Capsid Residue Controls Cytolysis and Apoptosis in Rhabdomyosarcoma Cells

Gullberg

Tolf

Jönsson

et al. 2010

J Virol

Self Cite

View full text Add to dashboard Cite

Coxsackievirus B2 (CVB2), one of six human pathogens of the group B coxsackieviruses within the enterovirus genus of Picornaviridae, causes a wide spectrum of human diseases ranging from mild upper respiratory illnesses to myocarditis and meningitis. The CVB2 prototype strain Ohio-1 (CVB2O) was originally isolated from a patient with summer grippe in the 1950s. Later on, CVB2O was adapted to cytolytic replication in rhabdomyosarcoma (RD) cells. Here, we present analyses of the correlation between the adaptive mutations of this RD variant and the cytolytic infection in RD cells. Using reverse genetics, we identified a single amino acid change within the exposed region of the VP1 protein (glutamine to lysine at position 164) as the determinant for the acquired cytolytic trait. Moreover, this cytolytic virus induced apoptosis, including caspase activation and DNA degradation, in RD cells. These findings contribute to our understanding of the host cell adaptation process of CVB2O and provide a valuable tool for further studies of virus-host interactions.Virus infections depend on complex interactions between viral and cellular proteins. Consequently, the nature of these interactions has important implications for viral cell type specificity, tissue tropism, and pathogenesis. Group B coxsackieviruses (CVB1 to CVB6), members of the genus Enterovirus within the family of Picornaviridae, are human pathogens that cause a broad spectrum of diseases, ranging from mild upper respiratory illnesses to more severe infections of the central nervous system, heart, and pancreas (61). These viruses have also been associated with certain chronic muscle diseases and myocardial infarction (2,3,12,13,22).The positive single-stranded RNA genome (approximately 7,500 nucleotides in length) of CVBs is encapsidated within a small Tϭ1, icosahedral shell (30 nm in diameter) comprised of repeating identical subunits made up of four structural proteins (VP1 to VP4). Parts of VP1, VP2, and VP3 are exposed on the outer surface of the capsid, whereas VP4 is positioned on the interior. The virion morphology is characterized by a star-shaped mesa at each 5-fold icosahedral symmetry axis, surrounded by a narrow depression referred to as the "canyon" (69). All six serotypes of CVB can use the coxsackie and adenovirus receptor (CAR) for cell attachment and entry (9,55,82). Some strains of CVB1, -3, and -5 also use decay accelerating factor ([DAF] CD55) for initial attachment to the host cell; however, binding to DAF alone is insufficient to permit entry into the cell (10, 54, 76).Picornaviruses are generally characterized by their cytolytic nature in cell culture. However, several in vivo and in vitro studies have shown that some picornaviruses, e.g., poliovirus, Theiler's murine encephalomyelitis virus, foot-and-mouth disease virus, CVB3, CVB4, and CVB5, may also establish persistent, noncytolytic infections (4,29,35,39,62,74). Recently, it has been shown that the diverse outcomes of picornaviral infections may depend on interactions between the viru...

show abstract

“…Virus viability was quantified by plaque titration on GMK cells, using gum tragacanth (Sigma) overlay as described for LV and other viruses (4,7).…”

Section: Cells and Virusesmentioning

confidence: 99%

“…We recently succeeded in adaptation of the LV prototype strain, 87-012, to cytolytically replicate to high titers in cell culture (7,17). This enabled studies of the composition, stability and host cell interactions of the LV virion.…”

mentioning

confidence: 99%

Physicochemical Properties of the Ljungan Virus Prototype Virion in Different Environments: Inactivated by Heat but Resistant to Acidic pH, Detergents and Non‐Physiological Environments Such as Virkon®‐Containing Solutions

Ekström¹,

Tolf²,

Edman³

et al. 2007

Microbiology and Immunology

Self Cite

View full text Add to dashboard Cite

It is of great importance to know how a virus particle is affected by environmental conditions. Physicochemical properties of the virion will affect the virus viability in different environments, viral transmission between hosts, and will also be important for safe handling of the virus. The physicochemical properties of the Ljungan virus (LV) prototype, 87-012, adapted to grow in cell culture were evaluated using both LV in crude cell extracts and purified virions. Replication of LV was completely inhibited by heat. Titers of LV were unaffected by acidic pH, reduced but not completely abolished by alkaline pH, and unaffected by exposure to the detergents Triton ® X-100 and SDS. Surprisingly, viable LV was still detected after incubation in the acidic, oxidising and detergent-containing environment produced by the commonly used disinfectant Virkon ® . In conclusion, LV is resilient to extreme pH, detergents and also to oxidising environments, but is sensitive to heat treatment.

show abstract

Replication of Ljungan virus in cell culture: The genomic 5′-end, infectious cDNA clones and host cell response to viral infections

Cited by 19 publications

References 65 publications

Duck Hepatitis A Virus Possesses a Distinct Type IV Internal Ribosome Entry Site Element of Picornavirus

Duck Hepatitis A Virus Possesses a Distinct Type IV Internal Ribosome Entry Site Element of Picornavirus

A Single Coxsackievirus B2 Capsid Residue Controls Cytolysis and Apoptosis in Rhabdomyosarcoma Cells

Physicochemical Properties of the Ljungan Virus Prototype Virion in Different Environments: Inactivated by Heat but Resistant to Acidic pH, Detergents and Non‐Physiological Environments Such as Virkon®‐Containing Solutions

Contact Info

Product

Resources

About