Principles of Molecular Virology STAGE / YEAR: 3 CREDITS: 10. PROGRAMME COMMITTEE: Biomedical Sciences. VERSION: 4th March 2015

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1 MODULE: MODULE NUMBER: JACS CODE: Principles of Molecular Virology BIO00041H C540 STAGE / YEAR: 3 CREDITS: 10 ORGANISER: Nathalie Signoret PROGRAMME COMMITTEE: Biomedical Sciences VERSION: 4th March 2015 TERM TAUGHT: Autumn 2015 PREREQUISITES: RECOMMENDATIONS: BIO00002I Immunology None SUMMARY: Viruses have been with us for millions of years evolving to survive and adapt to new host environments while driving the evolution of host genes. Diseases that are causally linked to viral infections are major contributors to morbidity and mortality in the animal and human populations globally. On the other hand, several viral infections are asymptomatic or only cause minor diseases. This module will examine overarching principles in molecular virology, addressing structural, molecular, and cellular biology aspects underpinning the fascinating interaction between viruses and the host. Focusing primarily on animal viruses, we will study key aspects of viral evolution, replication, and gene expression linked to infectivity that will be reviewed based on groundbreaking past discoveries and recent advances in research from published literature. AIMS: This module aims to (i) provide students with a thorough grounding in the concepts of virus biology, (ii) examine in greater depth assembly mechanisms and molecular viral strategies of replication and gene regulation, and (iii) explore the impact of viruses as tools for potential therapeutic exploitation using appropriate case studies rather than a systematic approach. LEARNING OUTCOMES: 1. Investigate viruses as distinct forms of living organisms: Highly structured particles with a protein core, protecting a nucleic acid genome, which make them infectious.

2 2. Assess viral molecular mechanisms from the replication cycle that are essential for the structural integrity, multiplication and propagation of viruses. 3. Explore the mechanisms employed by viruses to regulate expression of their own and host genes in order to achieve infection, persistence, and spreading. 4. Develop a coherent argument depicting the potential application of viral strategies towards disease control. RECOMMENDED READING: Reading associated with this module will come from published research papers the references will be given out at each lecture. SYNOPSIS OF TEACHING: Event Duration (Hrs) Topic Staff Room type Timing L Fundamental aspects of viruses as entities and infectious agents: introduction to the module, mapping of its content and what links the different lectures. Presenting the notion of viral evolution: leading to complexity and necessary adaptation to the host environment. Commonality, diversity and complementarities will be illustrated through case studies. L Viral structure: We will assess the biological reasons for the high degree of order and symmetry in the viral protein containers that encapsulate, and hence provide protection for, the viral genome, and review implications for viral evolution. The reasons for the occurrence of symmetry in viruses will be covered (based on Caspar & Klug's and Crick & Watson's seminal papers), followed by an explanation of Caspar and Klug s quasi equivalence theory and T numbers. Limitations of

3 the theory are assessed based on the example of the cancer causing papillomaviruses. Experimental techniques to determine virus structure, such as cryo EM and tomography, will also be discussed. Exercises will be used to help understand the mathematical principles for viral symmetry. L Viral assembly: We will focus on the assembly of a capsid, a key stage of the viral life cycle, and explore similarities and differences in RNA and DNA viruses. Different mechanisms of capsid assembly will be discussed, and differences between DNA and RNA viruses highlighted. For the case of RNA viruses the cooperative roles of the genomic RNA in capsid assembly will be analysed, including for example allosteric conformer switching mediated by interactions between coat protein and genomic RNA. From an experimental point of view, the use of mass spectrometry to investigate virus assembly and of single molecule fluorescence assays to monitor RNA conformation and virus assembly in real time will be covered. L Viral entry into a living cell: the key step that defines target specificity, appropriate viral material delivery and initiation of the replication cycle. Series of molecular interactions from the moment viruses get in contact with the host cell and the required viral material is delivered into the cell. Virus dependent strategies adapted to the type of infection and mode of virus Signoret

4 dissemination in the body, and linked to virus complexity. L Viral exit: Manufacturing new infectious particles to be released from infected cells. Virus specific routes to spread infection and favour host evasion. (cellular sites of viral assembly, host proteins and membrane incorporation, lysis, internal or surface budding, maturation, free and membrane bound particles, cell cell contact delivery). L Viral gene expression and regulation: Genomic architecture of RNA and DNA viruses. ssons from viral genomics. Mechanisms employed by viruses to regulate viral gene expression. Association of gene expression programs with specific stages of the viral lifecycle. L Virus host interactions: Regulation of host gene expression by viruses. Virus driven mechanisms of immune activation and escape. Viral proteins as archetypes of multifunctional master regulators of gene expression. L Exploitation of viral strategies for therapeutic approaches: dream or reality? Emphasis will be placed on cutting edge areas, where significant advances are being made, both in our understanding of molecular virology phenomena, and our ability to manipulate them by clinical interventions. This lecture will be in part student led. The students will participate in a debate or Signoret Signoret,,

5 presentation activity. This lecture will end with a summary of the main topics/themes in the module, giving students the opportunity to ask questions about material covered in the module. KEY TEXTS : These are available in EARL which is accessible through the VLE module site. ASSESSMENT : Formative: Summative: Re assessment: No 2 hour closed examination paper 2 hour closed examination paper DEMONSTRATING REQUIREMENTS: n/a MAXIMUM NUMBERS: limited by lecture room STUDENT WORKLOAD: students workload totalling 100 hours per 10 credit module ctures: 8 x 1.5 hours Workshops: 0 Supported learning sessions: 0 Practicals: 0 Tutorials: 0 Total Contact hours: 12 Assessments (formative and summative): 2 hr Private study: 84.5