Search results for "Viral Nonstructural Protein"

Parvovirus nonstructural protein 2 interacts with chromatin-regulating cellular proteins

2022

Autonomous parvoviruses encode at least two nonstructural proteins, NS1 and NS2. While NS1 is linked to important nuclear processes required for viral replication, much less is known about the role of NS2. Specifically, the function of canine parvovirus (CPV) NS2 has remained undefined. Here we have used proximity-dependent biotin identification (BioID) to screen for nuclear proteins that associate with CPV NS2. Many of these associations were seen both in noninfected and infected cells, however, the major type of interacting proteins shifted from nuclear envelope proteins to chromatin-associated proteins in infected cells. BioID interactions revealed a potential role for NS2 in DNA remodel…

Generalized Linear Model (GLM) framework for the association of host variables and viral strains with liver fibrosis in HCV/HIV coinfected patients

2012

Chronic hepatitis C virus (HCV) infection is the main cause of advanced and end-stage liver disease world-wide, and an important factor of morbidity and mortality in Human Immunodeficiency virus-1 (HIV-1) co-infected individuals. Whereas the genetic variability of HCV has been studied extensively in monoinfected patients, comprehensive analyses of both patient and virus characteristics are still scarce in HCV/HIV co-infection. In order to find correlates for liver damage, we sought to analyze demographic, epidemiological and clinical features of HCV/HIV co-infected patients along with the genetic makeup of HCV (viral subtypes and lineage studied by nucleotide sequencing and phylogenetic ana…

Effect of antiviral treatment and host susceptibility on positive selection in hepatitis C virus (HCV).

2007

Abstract We have conducted a large sequence study of the E1–E2 and NS5A regions of the HCV, subtypes 1a and b, both in patients previously treated with interferon, and untreated patients, who later responded, or not, to a combination therapy based on interferon plus ribavirin. We have examined the role played by the number of positively selected sites on disease progression and its relationship with several variables such as patients’ age, sex and their risk of acquiring the disease. We have detected three groups of patients that respond or not to combination therapy: responders of intermediate age, older non-responders and young non-responders, they possess an increasing average number of …

Trends for genetic variation of Hepatitis C Virus quasispecies in Human Immunodeficiency virus-1 coinfected patients

2007

Chronic infection by Hepatitis C Virus (HCV) causes liver fibrosis, which is accelerated by unknown mechanisms in patients with HIV-1 coinfection. The evolution of HCV quasispecies in this setting of coinfection is not fully understood. To compare HCV quasispecies between HIV-HCV coinfection and HCV monoinfection, we sequenced 340 HCV clones from the HVR-1 and NS3 regions at two different time points in two groups of treatment-naive patients with HCV-1a infection: (1) HIV-HCV positive (n=6); and (2) HIV negative-HCV positive (n=3). In HCV/HIV coinfection, we found a trend for reduced HCV genetic complexity and diversity, and a trend towards reduced dN/dS ratios in the HVR-1 region, especial…

Genetic variability of hepatitis C virus non-structural protein 3 and virus-specific CD8+ response in patients with chronic hepatitis C.

2004

Hepatitis C virus (HCV) variation in specific T-cell epitopes may represent a mechanism of viral persistence in chronic infection. We examined the HCV non-structural protein 3 (NS3), including the immunologically relevant epitopes HCV NS3-2 KLVALGINAV (human leukocyte antigen [HLA]-A2-restricted) and HCV NS3-1391 LIFCHSKKK (HLA-A3-restricted), in 22 HLA-A2+ patients with chronic infection. Significant amino acid variation was found in HCV NS3-2 epitope sequences when compared to the HCV-1 prototype virus. Six of the nine different HCV NS3-2 peptide variants were identified in patients with HCV NS3-2-specific CD8+ cells, detected with an HLA-A2 tetramer made with the HCV-1 prototype peptide.…

Humoral immune response to rotavirus NSP4 enterotoxin in Spanish children.

2005

The rotavirus non-structural protein 4 (NSP4) has been shown to play a crucial role in rotavirus-induced diarrhea, acting as a viral enterotoxin. It has also been demonstrated that antibody to NSP4 can reduce the severity of rotavirus-induced diarrhea in newborn mice. Two recombinant baculoviruses, expressing the NSP4 protein from the SA11 and Wa rotavirus strains, genotypes A and B, respectively, were used to produce and purify these glycoproteins, which were applied as antigen in an enzyme-linked immunosorbent assay (ELISA) to test the specific antibody response to NSP4 in human sera. Serum samples from 30 children convalescing from a rotavirus infection, from 54 healthy children under 5-…

Determinants of Substrate Specificity in the NS3 Serine Proteinase of the Hepatitis C Virus

1997

AbstractProcessing of the nonstructural polyprotein of the hepatitis C virus (HCV) requires the serine-type proteinase located in the amino-terminal domain of NS3. To identify residues within NS3 determining substrate specificity, a mutation analysis was performed. Using sequence alignments and three-dimensional structure predictions, amino acids assumed to be important for specificity were replaced and the enzymes were tested in an intracellulartrans-processing assay for their effects on cleavage of an NS4B-5B substrate. For some of the substitutions at positions 133, 134, 135, 136, 138, 152, 155, 157, and 169, slightly reduced processing efficiencies were observed but in no case was the s…

In vitro models for hepatitis C

2001

Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line.

1999

An estimated 170 million persons worldwide are infected with hepatitis C virus (HCV), a major cause of chronic liver disease. Despite increasing knowledge of genome structure and individual viral proteins, studies on virus replication and pathogenesis have been hampered by the lack of reliable and efficient cell culture systems. A full-length consensus genome was cloned from viral RNA isolated from an infected human liver and used to construct subgenomic selectable replicons. Upon transfection into a human hepatoma cell line, these RNAs were found to replicate to high levels, permitting metabolic radiolabeling of viral RNA and proteins. This work defines the structure of HCV replicons funct…

Substrate determinants for cleavage in cis and in trans by the hepatitis C virus NS3 proteinase

1995

Processing of the hepatitis C virus polyprotein is accomplished by a series of cotranslational and posttranslational cleavages mediated by host cell signalases and two virally encoded proteinases. Of these the NS3 proteinase is essential for processing at the NS3/4A, NS4A/4B, NS4B/5A, and NS5A/5B junctions. Processing between NS3 and NS4A occurs in cis, implying an intramolecular reaction mechanism, whereas cleavage at the other sites can also be mediated in trans. Sequence analysis of the amino termini of mature cleavage products and comparisons of amino acid residues around the scissile bonds of various hepatitis C virus isolates identified amino acid residues which might contribute to su…