scholarly journals Homoclinic and heteroclinic solutions to a hepatitis C evolution model

2018 ◽  
Vol 16 (1) ◽  
pp. 1537-1555 ◽  
Author(s):  
Tadas Telksnys ◽  
Zenonas Navickas ◽  
Romas Marcinkevicius ◽  
Maosen Cao ◽  
Minvydas Ragulskis
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Evolution Model ◽  
Coupling Coefficients ◽  
Heteroclinic Solutions ◽  
Existence Conditions ◽  
Generalized Differential ◽  
Necessary And Sufficient ◽  
Appl Math ◽  
Topological Sense

AbstractHomoclinic and heteroclinic solutions to a standard hepatitis C virus (HCV) evolution model described by T. C. Reluga, H. Dahari and A. S. Perelson, (SIAM J. Appl. Math., 69 (2009), pp. 999–1023) are considered in this paper. Inverse balancing and generalized differential techniques enable derivation of necessary and sufficient existence conditions for homoclinic/heteroclinic solutions in the considered system. It is shown that homoclinic/heteroclinic solutions do appear when the considered system describes biologically significant evolution. Furthermore, it is demonstrated that the hepatitis C virus evolution model is structurally stable in the topological sense and does maintain homoclinic/heteroclinic solutions as diffusive coupling coefficients tend to zero. Computational experiments are used to illustrate the dynamics of such solutions in the hepatitis C evolution model.

scholarly journals A Retention Signal Necessary and Sufficient for Endoplasmic Reticulum Localization Maps to the Transmembrane Domain of Hepatitis C Virus Glycoprotein E2

1998 ◽  
Vol 72 (3) ◽  
pp. 2183-2191 ◽  
Author(s):  
Laurence Cocquerel ◽  
Jean-Christophe Meunier ◽  
André Pillez ◽  
Czeslaw Wychowski ◽  
Jean Dubuisson
Keyword(s):  
Endoplasmic Reticulum ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Transmembrane Domain ◽  
Intracellular Localization ◽  
Native Form ◽  
Glycosyl Phosphatidylinositol ◽  
Er Retention ◽  
Er Targeting ◽  
Necessary And Sufficient

ABSTRACT The hepatitis C virus (HCV) genome encodes two envelope glycoproteins (E1 and E2). These glycoproteins interact to form a noncovalent heterodimeric complex which is retained in the endoplasmic reticulum (ER). To identify whether E1 and/or E2 contains an ER-targeting signal potentially involved in ER retention of the E1-E2 complex, these proteins were expressed alone and their intracellular localization was studied. Due to misfolding of E1 in the absence of E2, no conclusion on the localization of its native form could be drawn from the expression of E1 alone. E2 expressed in the absence of E1 was shown to be retained in the ER similarly to E1-E2 complex. Chimeric proteins in which E2 domains were exchanged with corresponding domains of a protein normally transported to the plasma membrane (CD4) were constructed to identify the sequence responsible for its ER retention. The transmembrane domain (TMD) of E2 (C-terminal 29 amino acids) was shown to be sufficient for retention of the ectodomain of CD4 in the ER compartment. Replacement of the E2 TMD by the anchor signal of CD4 or a glycosyl phosphatidylinositol (GPI) moiety led to its expression on the cell surface. In addition, replacement of the E2 TMD by the anchor signal of CD4 or a GPI moiety abolished the formation of E1-E2 complexes. Together, these results suggest that, besides having a role as a membrane anchor, the TMD of E2 is involved in both complex formation and intracellular localization.

scholarly journals Hyperphosphorylation of the Hepatitis C Virus NS5A Protein Requires an Active NS3 Protease, NS4A, NS4B, and NS5A Encoded on the Same Polyprotein

1999 ◽  
Vol 73 (12) ◽  
pp. 9984-9991 ◽  
Author(s):  
Petra Neddermann ◽  
Angelica Clementi ◽  
Raffaele De Francesco
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protease Activity ◽  
Nonstructural Protein ◽  
Kinetic Studies ◽  
Stable Complex ◽  
Polyprotein Processing ◽  
Total Inhibition ◽  
Necessary And Sufficient ◽  
Ns3 Protease

ABSTRACT The nonstructural protein NS5A of hepatitis c virus (HCV) has been demonstrated to be a phosphoprotein with an apparent molecular mass of 56 kDa. In the presence of other viral proteins, p56 is converted into a slower-migrating form of NS5A (p58) by additional phosphorylation events. In this report, we show that the presence of NS3, NS4A, and NS4B together with NS5A is necessary and sufficient for the generation of the hyperphosphorylated form of NS5A (p58) and that all proteins must be encoded on the same polyprotein (in cis). Kinetic studies of NS5A synthesis and pulse-chase experiments demonstrate that fully processed NS5A is the substrate for the formation of p58 and that p56 is converted to p58. To investigate the role of NS3 in NS5A hyperphosphorylation, point and deletion mutations were introduced into NS3 in the context of a polyprotein containing the proteins from NS3 to NS5A. Mutation of the catalytic serine residue into alanine abolished protease activity of NS3 and resulted in total inhibition of NS5A hyperphosphorylation, even if polyprotein processing was allowed by addition of NS3 and NS4A in trans. The same result was obtained by deletion of the first 10 or 28 N-terminal amino acids of NS3, which are known to be important for the formation of a stable complex between NS3 and its cofactor NS4A. These data suggest that the formation of p58 is closely connected to HCV polyprotein processing events. Additional data obtained with NS3 containing the 34 C-terminal residues of NS2 provide evidence that in addition to NS3 protease activity the authentic N-terminal sequence is required for NS5A hyperphosphorylation.

scholarly journals Amphipathic Helix-Dependent Localization of NS5A Mediates Hepatitis C Virus RNA Replication

2003 ◽  
Vol 77 (10) ◽  
pp. 6055-6061 ◽  
Author(s):  
Menashe Elazar ◽  
Kwang Ho Cheong ◽  
Ping Liu ◽  
Harry B. Greenberg ◽  
Charles M. Rice ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Dependent Manner ◽  
Amphipathic Helix ◽  
Nonstructural Proteins ◽  
Hepatitis C Virus Rna ◽  
Peptide Mimic ◽  
Virus Rna ◽  
Necessary And Sufficient ◽  
Dose Dependent

ABSTRACT We identified an N-terminal amphipathic helix (AH) in one of hepatitis C virus (HCV)’s nonstructural proteins, NS5A. This AH is necessary and sufficient for membrane localization and is conserved across isolates. Genetically disrupting the AH impairs HCV replication. Moreover, an AH peptide-mimic inhibits the membrane association of NS5A in a dose-dependent manner. These results have exciting implications for the HCV life cycle and novel antiviral strategies.

HEPATITIS C VIRUS INFECTION (AND ADDITIONAL NEOPLASMS) AMONG MARGINAL ZONE LYMPHOMAS

1997 ◽  
Vol 96 (2) ◽  
pp. 427-428 ◽  
Author(s):  
FREDERICO SILVESTRI ◽  
GIOVANNI BARILLARI ◽  
RENATO FANIN ◽  
FLAVIA SALMASO ◽  
LAURA INFANTI ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Marginal Zone ◽  
Hepatitis C Virus Infection

Public health challenges in hepatitis C virus infection

2000 ◽  
Vol 15 (5 (Suppl.)) ◽  
pp. E83-E90 ◽  
Author(s):  
John M Kaldor ◽  
Gregory J Dore ◽  
Patricia Kl Correll
Keyword(s):  
Public Health ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Hepatitis C Virus Infection ◽  
Public Health Challenges

Expression of CD81, am ligand for hepatitis C virus (HCV) is increased on CD5+ B-lymphocytes but may not be the receptor for internalisation of HCV

2001 ◽  
Vol 120 (5) ◽  
pp. A552-A552
Author(s):  
M CURRY ◽  
T DEIGNAN ◽  
P COSTELLO ◽  
L GOLDENMASON ◽  
M DUFFY ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Lymphocytes
Sign in / Sign up

Export Citation Format

Share Document