Medical Virology  I. General Virology.  II. System Virology.  1- DNA viruses. 2- RNA viruses.

General Medical Virology  Medical Virology: study of viruses that cause human infection.  Viruses are the smallest infectious agents, having a nm diameter.  Also known as submicroscopic infectious entities.  The term filterable agent applied to viruses, because they can pass through 0.22 um filter that retain other microbes.  Activity: Obligate intracellular parasite, inert in extra- cellular environment, and require living cells to support its replication.  Structure: Complexes of only one type of nucleic acids ( either DNA or RNA ). proteins (capsid), some are surrounded by lipid- containing membrane (envelope).

Definitions in virology:  Genome: nucleic acid (RNA or DNA).  Capsid: protein coat that encloses the nucleic acid genome. (Protection, attachment).  Capsomere: morphological unite of the capsid seen by EM, each of which is made up of one or more polypeptide chains.  Envelope: lipid containing membrane that surround some virus particles, derived from host cells.  Naked viruses: Viruses without an envelope are known as naked viruses.  Nucleocapsid: the protein- nucleic acid complex representing the packaged form of the viral genome.  Virion: complete infective viral particle. Nucleocapsid ( Parvoviruses, Picornaviruses). Nucleocapsid plus a surrounding envelope (Herpesvisuses, Orthomyxoviruses)

General Characteristics of viruses: 1- Size: smallest infectious agents ( 20 to 300 nm in diameter), seen by EM. 2- Location: Obligate intracellular parasites. 3- Genome: only single type of NA either ( DNA, RNA ). 4- Specific structures: nucleic acid is enclosed in protein shell (capsid), may contain envelope. 5- Parasitic mechanism: (The viruses are not capable of self replication). They are parasitic at the genetic level, they compromise the machinery function of the infected cells and shift them to produce viral particles. 6- Drugs: Not affected by antibiotics, affected by antiviral drugs and interferones.

Chemical composition of viruses include: I- Viral nucleic acid. II-Viral capsid. III-Viral envelope. IV-Viral proteins.

I. Viral nucleic acid (Genome ):  The virus contain single kind of nucleic acid either RNA or DNA, code for genetic information necessary for replication of the virus.  The genome may be single stranded or double stranded, circular or linear, segmented or non segmented.  The size of viral genome:  DNA genome range from 3.2 kbp (hepadnaviruses) to 375 kbp( poxviruses).  The viral RNA range from about 7 kb ( picornaviruses) to 30 kb ( coronaviruses ).  The sequences and composition of nucleotides of each viral nucleic acid are distinctive.

II- Viral capsid  Symmetric protein shell that surround the viral NA in the core, and its protect the viral NA, and in naked viruses its important in the adsorption to host cell receptors & penetration.  Capsids are composed of varying numbers of capsomers ( morphological units), each of which is made up of one or more polypeptide chains.  Architecture of a virion is strongly influenced by the symmetry of viral capsid.  Three types of symmetry 1. Helical 2. Cubic ( icosahedral) 3. Complex

Helical nucleocapsid symmetry  Here the nucleic acid of the virus has a spring like or screw like flexible configuration( helical), and the capsid protein is condensed on the helical nucleic acid.  Helical symmetry give the virus a rod like appearance.  Medical important human viruses do not exist as naked helical nucleocapsids.  So all human viruses with helical symmetry are enveloped and include orthomyxoviruses, paramyxoviruses, rhabdoviruses, filoviruses, areaviruses, coronaviruses and bunyaviruses.

Icosahedral nucleocapsid symmetry  N.A. is surrounded by capsomeres arranged in icosahedrons ( i.e. a solid structure with 12 vertices, 20 equilateral triangular faces, and 30 edges).  Icosahedral viruses have a sphere like appearance.  Viruses with icosahedral symmetry includes: parvoviruses, papovaviruses, adenoviruses, picornaviruses, calciviruses and reoviruses.  Most viruses with icosahedral symmetry are naked; exceptions include hepadnaviruses, herpesviruses, togaviruses, and flaviviruses.

Complex symmetry  Viruses that cannot be categorized as having helical or icosahedral symmetry are complex.  Viruses are considered complex if they have complex structures, such as poxviruses, or if they have two types of nucleocapsid symmetry ( helical and cubic) such as retroviruses.

III. Viral envelope:  A number of viruses contain lipid envelopes as part of their structure.  The envelope is derived from host cellular membrane and is acquired by the virus during the late stages of replication as the progeny virus undergoes budding.  Composition the envelope consist of a lipid bilayer derived from the cellular membrane and viral-coded glycoproteins, which are inserted in the bilayer and project to the outer surface.  These glycoprotein serve two basic functions:  1- They promote interaction with nucleocapsid proteins, which is essential for the final stages of viral assembly.  2- They mediate attachment to cellular receptors, which is essential for the infectivity.  Denaturation : organic solvents and detergents dissolve the envelope, causing the particle to lose its infectiveness.

IV-Viral proteins : can be classified into : 1.Structural proteins: are essential for the formation of infective viral particles. a- some proteins are associated with the nucleic acid and are responsible for proper packing of viral genomes. b- other form the protective layer of the virus. 2. Membrane or matrix protein A restively hydrophobic protein located on the inside of viral envelope of many enveloped RNA viruses. This protein is located beneath the external spike proteins of viral envelope and beneath the plasma membrane of RNA virus producing cell. The viral nucleocapsid interacts with the matrix protein in budding through the host cell membrane. 3. Spike proteins ( glycoprotein) Viral coded envelope glycoproteins that project from the envelope surface. These protein may have functions such as hemagglutination or neuraminidase activity or promote cell membrane fusion.

4. Enzymes: a- Viral polymerases are essential for nucleic acid replication. b- Proteases are used by the viruses to: I- process large transcripts into small functional proteins. II- help release nucleic acid from the nucleocapsid. c- Endonuclease and ligases are specific enzymes that some viruses required for replication.

Virus shapes and its detail structures:  Non enveloped (Icosahedral) Enveloped

Taxonomic classification of viruses is based on: 1- Nucleic acid type: Family: viridae, Subfamily: virina, Genus: virus.  Examples on viral families:  I. DNA viruses:  Parvoviridaes: sDNA, parvovirus B19.  Papovaviridae: dsDNA, Papillomavirus  Adenoviridae: dsDNA, Adenovirus.  Herpesviridae: dsDNA, Herpes simplex.  Poxviridae: dsDNA, poxvirus.  Hepadnaviridae: dsDNA, Hepatitis B.

 II. RNA viruses:  Paramyxoviridae: ssRNA, Respiratory syncytial.  Orthomyxoviridae: ssRNA, Influenza.  Coronaviridae: ssRNA, Coronaviruses.  Picornaviridae: ssRNA, Rhinovirus.  Rhabdoviridae: ssRNA, Rabies.  Arenaviridae: ssRNA, Lassa fever.  Bunyaviridae: ssRNA, Hanta virus.  Caliciviridae: ssRNA, Norwalk virus.  Filoviridae: ssRNA, Marburg.  Flaviviridae: ssRNA, Yellow fever.  Retroviridae: ssRNA, HIV.  Togaviridae: ssRNA, Rubella.  Reoviridae : dsRNA, Rotavirus.

2- Physiochemical properties of the virion, including molecular mass, buoyant density, pH stability, thermal stability, and susceptibility to physical and chemical agents, especially ether and detergents. 3-Enveloped or naked virion This property is combined with symmetry, five different morphological forms of viruses are delineated: (1) Naked icosahedral. Parvo,Papova,Adeno,Picorna,Calci and Reoviridae. (2) Enveloped icosahedral. Herpes,Hepadna,Toga and Flaviviridae. (3) Naked helical. Medical important human viruses do not exist as naked helical nucleocapsids. (4) Enveloped helical. Orthomyxo, Paramyxo, Rhabdo, Filo, Corona, Arena and Bunyaviridae. (5) Complex. Pox and Retroviridae. 4- Biological properties including natural host range, mode of transmission, vector relationships, pathogenicity, tissue tropisms, and pathology.

5-Current classification: The five basic subgroups of viral families have been derived by combing the important characteristics of:  Nucleic acid type.  Symmetry.  Naked versus enveloped morphology. Group I DNA viruses with icosahedral symmetry and naked Parvoviridae,Papovaviridae, and Adenoviridae. Group II DNA viruses with complex coat or envelopes. Herpeviridae, Hepadnaviridae, and Poxviridae. Group III RNA viruses with icosahedral symmetry Picornaviridae, Caliciviridae, Reoviridae, Togaviridae, and Flaviviridae Group IV RNA viruses with helical symmetry Orthomyxoviridae, Paramyxoviridae, Rhabdoviridae, Filoviridae, Arenaviridae, Coronaviridae, and Bunyaviridae Group V RNA viruses with mixed or complex symmetry Retroviridae

Virus-Like Agents  Prions: infectious particles composed solely of protein with no detectable nucleic acid. Highly resistant to heat, formaldehydes and ultraviolet. Disease: transmissible spongiform encephalopathies include: Mad cow disease (cattle). Creutzfeldt Jakob disease (human).  Viroids: infectious particles composed of nucleic acid without protein coat. RNA only e.g. hepatitis D virus.