Medical Virology Lecture Notes PDF

1. Some General Concepts: Viruses contribute significantly to the global burden of infectious diseases. Most of the diseases are mild, but viruses may cause severe diseases in susceptible individuals, such as the mal-nourished, immuno-compromised, the very old and the very young. What is a virus ?...

1. Some General Concepts: Viruses contribute significantly to the global burden of infectious diseases. Most of the diseases are mild, but viruses may cause severe diseases in susceptible individuals, such as the mal-nourished, immuno-compromised, the very old and the very young. What is a virus ?  Very simple structures consisting essentially of a nucleic acid genome, protected by a shell of protein.  May or may not have a lipoprotein envelope.  Has no organelle.  Very small, sizes range 20 - 200 nm, beyond the resolving power of the light microscope.  Metabolically inert and can only replicate inside a host cell.  Genome consists of ONLY one type of nucleic acid; either RNA or DNA.  Viral genome codes for the few proteins necessary for replication: some proteins are non-structural e.g. polymerase, and some are structural, i.e. form part of the virion structure. 2. Terminology Virion: Infectious virus particle. Capsid: Protein shell which surrounds and protects the genome. It is built up of multiple (identical) protein sub-units called capsomers. Capsids are either icosahedral or tubular in shape. Nucleocapsid: Genome + capsid. 1 Envelope: Lipoprotein membrane which surrounds some viruses, derived from the plasma membrane of the host cell. Glycoproteins: Proteins found in the envelope of the virion; usually glycosylated. 3. Classification of Viruses: Viruses are mainly classified by phenotypic characteristics, such as morphology, nucleic acid type, mode of replication, host organisms, and the type of disease they cause. Morphology: Helical morphology is seen in many filamentous and pleomorphic viruses. Icosahedral morphology is characteristic of many “spherical” viruses. The number and arrangement of the capsomeres (morphologic subunits of the icosahedron) are useful in identification and classification. Many viruses also have an outer envelope. Chemical Composition and Mode of Replication: The genome of a virus may consist of DNA or RNA, which may be single stranded (ss) or double stranded (ds), linear or circular. The entire genome may occupy either one nucleic acid molecule (monopartite genome) or several nucleic acid segments (multipartite genome). The different types of genome necessitate different replication strategies. A classification places viruses into one of seven groups depending on a combination of their nucleic acid (DNA or RNA), strandedness 2 )single-stranded or double-stranded), Sense, and method of replication. Classification of viruses: Viruses can be placed in one of the seven following groups: A. dsDNA viruses (e.g. Adenoviruses, Herpesviruses, Poxviruses( B. ssDNA viruses (+ strand or “sense”) DNA (e.g. Parvoviruses) dsRNA viruses (e.g. Reoviruses( C. (+)ssRNA viruses (+ strand or sense) RNA (e.g. Picornaviruses, Togaviruses( D. (−)ssRNA viruses (− strand or antisense) RNA (e.g. Orthomyxoviruses, Rhabdoviruses) E. ssRNA-RT viruses (+ strand or sense) RNA with DNA intermediate in life-cycle (e.g. Retroviruses) F. dsDNA-RT viruses (e.g. Hepadnaviruses( 3 4. Atypical Virus Like Particles: There are four exceptions to the typical virus as described previously: Defective viruses: Composed of viral nucleic acid and proteins, but cannot replicate without a helper virus. Pseudoviruses: Contain host DNA instead of viral DNA. Viriods: Consist of a single molecule of circular RNA with no protein coat or envelope. Prions: Smallest known infectious particles. 5. Viral Replication: Viruses are totally dependent on a host cell to replicate. While the sequence and period of events varies somewhat from virus to virus, the general strategy of replication is similar: a. Adsorption (attachment): Highly specific, the surface of the virion contains structures that interact receptors on the surface of the host cell. It defines and limits the host species and type of cell that can be infected by a particular virus. Damage to the binding sites on the virion or blocking by specific antibodies (neutralization) can render virions non-infectious. b. Uptake (Penetration): The process whereby the virion enters the cell; as a result of fusion of the viral envelope with the plasma membrane of the cell or endocytosis. c. Uncoating: The protein coat of the virion dissociates and the viral genome is released into the cytoplasm. 4 d. Early phase: Transcription of viral mRNA and translation of a number of non-structural ("early") proteins takes place. e. Genome replication: Multiple copies of the viral genome are synthesized by a viral polymerase. f. Late phase: Transcription and translation of viral mRNA and synthesis of the structural "late" proteins which are needed to make new virions. g. Assembly (of new virions): The proteins self-assemble and a genome enters each new capsid. This takes place either in the nucleus or in the cytoplasm of the cell, or sometimes, just beneath the cell surface. h. Release of progeny virions: Release of new infectious virions is the final stage of replication. This may occur either by budding from plasma membrane (for enveloped viruses), or else by disintegration (lysis) of the infected cell (for non-enveloped viruses). Some viruses use the secretory pathway to exit the cell. 5 6. How do Viruses Cause Diseases? Viruses are capable of infecting all types of living organisms from bacteria to humans. Cell tropism: A major factor that controls which cell type a virus can infect; presence of the appropriate receptor on the cell surface, to which the virus must attach in order to gain entry into the cell. Viruses enter the body: By inhalation, ingestion, sexually, parenteral or inoculation through the skin or mucous membranes. Infection may also sometimes be passed from a mother to her fetus transplacentally (vertical transmission). Type of infection: May either remain localized to the site of entry, or it may cause a disseminated infection according to the site of target. Virus replicates initially at the site of entry, but then enters the blood (viraemia) or lymphatics and spreads throughout the body.Other viruses may replicate locally initially, and then enter nerve endings and travel up the axon to infect the central nervous system. Incubation period: Time from exposure to an organism to the onset of clinical disease. Viruses that cause localized infections have short incubation periods (