Content

1. Historical overview of Virology

Hypotheses about the maintenance of life and spontaneous generation. The work of Pasteur. Microscopic infectious agents and Koch's postulates. The nineteenth century: the discovery of viruses. The tobacco mosaic virus: the concept of "filtrable infectious agent". Discovery of animal viruses. The twentieth century: characterization, chemical and genetic structure of viruses. Significant events in the history of virology. The eradication of smallpox and the risk of re-emergence. Clinical aspects of virology and biotechnology. Bioterrorism.

 

2. An introduction to viruses and Virology

The world of viruses. Strict parasitism, multiplication and transmission. The viral disease and the concept of "iceberg". Viral diversity. The viral particle: size, chemical composition, morphology and nomenclature. Functions of the capsid, stability and recognition. Chemical composition, structure and organization of the viral genome: structural and non-structural genes. The polarity of the nucleic acid. The viral cycle: extracellular and intracellular phases. Virus multiplication: productive and non-productive infection. Sequential expression of viral genes. Viruses, mobile genetic elements and living beings.

 

3. Structure of viral particles

Morphology of viral particles. Architectural study of viral particles: electron microscopy and three-dimensional reconstructions. X-ray diffraction: level of resolution. Molecular architecture in helical and icosahedral symmetries. Trans-membrane proteins in viral envelopes. Receptor binding sites. Viral antigens and epitopes B and T. Neutralization and evasion of neutralization. Genetic and epitope variability. Other structural components of viruses.

 

4. Viral multiplication

Cell recognition. Nature and function of receptors. Internalization. Uncoating. The cellular shutdown. Stimulation of cellular functions: papillomavirus, polyomavirus and adenovirus. Synthesis of RNA, DNA and viral proteins: temporal sequences. Cytopathic effects. Exit of viral particles with and without lysis. Apoptosis. Cellular transformation in RNA virus: cellular oncogenes, activation and transduction. Cellular transformation in DNA virus: viral oncogenes and oncoproteins. Processing of viral proteins. Targets for antiviral drugs. RNA interference.

 

5. Principles of viral taxonomy

First virus classifications: Baltimore classification of animal viruses. The International Committee on Taxonomy of Viruses and the classification system. Viral properties used in taxonomy. Families of animal viruses and viruses not yet classified. Nomenclatural changes. The main human pathogens and their diseases.

 

6. Genetics and viral genomes

Diversity of viral genomes. Principle of economy and complexity of viral genomes; overlapping genes. Segmented and split genomes. Information encoding the viral genome. Types of viral genomes: gene expression and replication strategy for each type; temporal regulation strategies. The infectious clone. Principles of reverse genetics. Defective viruses.

 

7. Virological methodology

Obtaining viral particles. Cell culture. Small and medium scale cultures. Purification. Quantitative and qualitative analysis of viral particles. Detection of viral components and applications in diagnostic methodology. The Virology laboratory: areas and distribution. Biological safety. Containment levels: P1 to P4. Air treatment. Effluent treatment.

 

8. Response to viral infections and vaccines.

Types of vaccines; attenuated and inactivated. Molecular basis of attenuation. New generation of vaccines. Recombinant vaccines and synthetic peptides. Vaccination with nucleic acids. New vectors in vaccines. SARS-CoV-2 vaccines. Herd immunity. Innate and adaptive immune response. Sentinel cells, complement, inflammation, interferons. Communication between innate and adaptive response. Adaptive immune response: humoral and cellular. The importance of the antiviral cellular immune response. The bacterial immune system CRISPR/Cas9.

 

9. Pathogenesis of viral infections.

"Good" viruses. Virus-host coexistence. Asymptomatic infections. Characteristics of viral infections. Gates of entry. Transmission routes: horizontal and vertical. Localized and systemic infections. Dissemination. Viremia. Nerve transmission. Target tissues: tropism. Acute and persistent infections. Latent infections. Viral and non-viral factors influencing pathogenesis. Virulence. Evasion of the immune response by the virus. Immunopathology.

 

10. Origin and evolution of viruses

Origin of viruses and regressive theories for a cellular origin. Mechanisms of generation of diversity. Mutation frequencies and relative abundance of mutants. Fixation of mutations. Viral replicases and copying fidelity. Variability and evolution in RNA viruses and retroviruses. The viral quasispecies. Evolution and evolutionary potential. Darwinian selection and Darwinian mutations. Founding effects and bottlenecks. Genetic and antigenic divergence, the influenza virus. 

 

11. Emerging viruses and viral diseases

Emergence of new viral diseases. Host jump and viral reservoirs. Viral emergence and viral re-emergence. Environmental factors, social and technological factors. Importance of arthropod vectors. The human species as a terminal host. New emerging viruses and human viruses. Haemorrhagic fevers. The Ebola virus and human immunodeficiency virus, poxvirus and coronavirus. The continuing re-emergence of influenza virus and others. The virome.

 

12. Peculiar infectious agents

The prion: Infectious proteins. Development of the prion concept. The amyloid. Synthesis and processing of PrP^c. PrP^sc formation and propagation of prions. Spongiform encephalopathies: inheritance and contagion. Phenotypic diversity of prions; strains. The "scrapie" and bovine spongiform encephalopathy. Interspecific barriers. The human spongiform encephalopathies: Kuru, Creutzfeldt-Jakob disease and hereditary diseases. Prions in yeast. Viroids: structure and consistency of domains. Possible pathogenetic mechanisms. The satellites. The hepatitis delta virus. The virophages.

 

13. Bacteriophages

Use of bacteriophages in molecular genetics and biotechnology. The "Phage Display". The generation of antibodies without immunization and the search for new ligands. Directed molecular evolution. Systems of selection of antiviral drugs: the case of protease inhibitors.

 

14. Artificial viruses

Viruses as new manipulable nanomaterials. Viral gene therapy: important features and biological risks. Gene therapy products on the market. Artificial viruses as alternatives to viral gene therapy. Types of artificial viruses and biomolecules used. Modular strategies. Selection of virus-inspired functional domains. Examples and applications of artificial viruses.