Download PDF Structure Based Study of REPLICATION VIRAL by R Holland Cheng

Sinopsis

Human rhinoviruses (HRVs) are small, icosahedral, non-enveloped, singlestranded positive-sense RNA viruses. Out of the 74 type A serotypes 12, the minor group bind members of the LDL receptor-family; the remainder plus all the 25 type B HRVs bind intercellular adhesion molecule-1. HRVs enter cells by receptor-mediated endocytosis. The ensuing structural modifications lead to release of the viral RNA into the cytosol where virus replication takes place. Binding to plasma membrane receptors, entry into the cell, uncoating, and penetration of the viral genome are discussed with respect to receptor and virus structure. Despite high structural similarity, major and minor group HRVs, as well as the individual major group serotypes, differ with respect to the process of entry and uncoating.

Since the isolation of a common cold virus from nasal mucus and its propagation in tissue culture,1 much has been learned about the replication cycle of these small, icosahedral, single-stranded positive-sense RNA viruses termed “human rhinoviruses” (HRVs). Much knowledge stems from earlier studies of the related enteroviruses, in particular the polio virus and coxsackie virus, which are rather closely related to HRVs; with due care, insight gained from work on enteroviruses can often, but not always, be extrapolated to the rhinovirus field. Physicochemically, rhinoviruses are distinguished from enteroviruses based on their acid lability, a feature originally used for their classification; enteroviruses, in contrast, remain infective at pH below 3; thus, they can pass unharmed through the digestive tract. They infect the intestinal epithelia and sometimes spread throughout the body, causing viremia. Conversely, rhinoviruses are comparably harmless, usually remaining confined to the upper respiratory tract and only occasionally spreading to the lungs.

During the HRV infection cycle, the following sequence of events can be differentiated: (1) virus binding to its receptors at the plasma membrane; (2) entry into the cell by receptor-mediated endocytosis; (3) conformational change of the viral capsid; (4) release of the viral RNA (“uncoating”); (5) RNA penetration into the cytoplasm; (6) synthesis of viral proteins; (7) RNA replication; and (8) assembly and release of new, infectious virions.

HRVs are composed of a protein shell assembled from 60 copies each of the four capsid proteins VP1, 2, 3, and 4. VP4 is internal and in close proximity to the RNA; however, due to the dynamic nature of the capsid, large parts of VP4 and the capsid-internal N-terminus of VP1 become temporally exposed to the solvent, a feature termed “breathing.”2–6 The viral shell is about 30 nm in diameter with the five-fold axes of icosahedral symmetry being surrounded by a cleft, termed the canyon. It encloses a single-stranded RNA genome of roughly 7100 bases. Upon arrival in the cytosol, the RNA becomes translated into a polyprotein that is autocatalytically and co-translationally cleaved by the viral proteinases 2Apro, 3Cpro and 3CDpro into VP1, VP0, VP3 and the non-structural proteins. Maturation cleavage of VP0 into VP2 and VP4 occurs by an unknown protease upon virus assembly. Not counting the precursor proteins — such as 3CD, the precursor of the protease 3Cpro and the RNA-dependent RNA polymerase 3Dpol — 11 mature polypeptides are eventually generated from the polyprotein

Content

1. Human Rhinovirus Cell Entry and Uncoating
2. Role of Lipid Microdomains in Influenza 43  Virus Multiplication
3. Functions of Integrin α 2β 1, A Collagen Receptor, in the Internalization of Echovirus
4. Entry Mechanism of Murine and SARS 77 Coronaviruses — Similarity and Dissimilarity
5. Hepatitis Viruses, Signaling Events and Modulation of the Innate Host Response
6. Virus-Cell Interaction of HCV
7. RNA Replication of Hepatitis C Virus
8. Structure and Dynamics in Viral RNA Packaging
9. Rational Design of Viral Protein Structures with Predetermined Immunological Properties
10. Bioinformatics Resources for the Study of Viruses at the Virginia Bioinformatics Institute
11. Virus Architecture Probed by Atomic Force Microscopy
12. Filovirus Assembly and Budding
13. Challenges in Designing HIV Env Immunogens for Developing a Vaccine
14. Insights into the Caliciviridae Family
15. Mathematical Approaches for Stoichiometric Quantification in Studies of Viral Assembly and DNA Packaging
16. Virus-like Particles of Fish Nodavirus
17. The Assembly of the Double-Layered Capsids of Phytoreo viruses
18. Structure and Assembly of Human Herpesviruses: New Insights From Cryo- Electron Microscopy and Tomography
19. Human Papillomavirus Type 16 Capsid Proteins: Immunogenicity and Possible Use as Prophylactic Vaccine Antigens
20. Chimeric Recombinant Hepatitis E Virus- like Particles Presenting Foreign Epitopes as a Novel Vector of Vaccine by Oral Administration
21. Nucleocapsid Protein of Hantaviruses (Bunyaviridae): Structure and Functions
22. Astrovirus Replication: An Overview
23. DNA Vaccines against Viruses
24. Life Cycles of Polyomaviridae — DNA Tumor Virus

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