Mircrobiology Lecture - 18 Viruses

Viruses

Kingdom Vira

General properties of viruses. Virus

contain only one type of nucleic acid (RNA or DNA) as their genome. Virus particles replicates only in living cells and therefore are obligate intracellular parasites at the genetic level. Viruses do not have cellular organization. They back the enzymes necessary for protein synthesis and are dependent for translation on the biosynthetic machinery of host cell (ribosomes).

Viruses

multiply by a complex process (replication) and not by binary fission. Viruses are the smallest infection agents (20-300 nm). They are invisible with the light microscope. Viruses are unaffected by antibacterial antibiotics. Viruses can infect all kind of unicellular organisms (animals, plants, procaryotic and eucariotic microorganisms).

Defective viruses Defective virus is a virus particle that is functionally deficient in some aspect of replication. 1. Defective interfering particles (DIP). They are deletion mutants which lacks a portion of its genome but contain normal capsid proteins, they require infections homologous virus as helper for replication.

2.Satellite This category of defective virus requires an unrelated replication geterologous- competent virus as helper.  Examples: - adenoassociated - delta agent (hepatitis D virus, co-infection hepatitis B virus). 3.Pseudovirions Defective particle which contain only host cell DNA and capsid.

Viroids Small

infection agents that cause diseases of plants. They are NA molecules without a protein coat. Plant viroids are single-stranded, covalently closed, circular RNA molecules, consisting of about 360 nucleotides. Viroid RNA does not encode any protein products.

Prions

Prions

are differ from both viruses and viroids in that they consist of protein and not nucleic acid.

The

prion protein (PrP) is encoded by the host’s chromosomal DNA. The normal form of the protein (PrPc) is expressed on the surface of neurons both infected and uninfected brains. An abnormal isoform of this protein (PrPsc)- is a post-translationally modified normal host form, which is insoluble in detergents and resistant to proteases. Proteins are extremely resistant to inactivation by UV light and ionizing radiation.

Prion’s

diseases is a group of human and animal fatal neurodegenerative diseases. Histologically, all prions diseases, are characterized by spongiform vacuolization in the central nervous system, the accumulation of a unique protein in cytoplasmic vesicles of neurons, the formation of extracellular amyloid plaques, composed of PrPsc. The incubation period of ″slow″ prion diseases is long (years).

A unique

characteristic of the prion diseases is that there is no immune response, no inflammatory reaction in the diseased tissue. Animal diseases: Scrapie of sheep Bovine spongiform encephalopathy of cattle (″mad cow disease″). Transmissible mink encephalopathy.

Human

diseases: 2.Crentzfeldt- yakob disease (sporadic, familial, acquired-iatrogenic) 3.Gerstmann-Stranssler-Scheinker syndrom 4.Fatal familial insomnia. 5.Kuru (related to ritualistic cannibalism in Papua New Guinea).

GENERAL STRUCTURE OF A NONENVELOPED (NAKED) VIRUS.

Structure of a nonenveloped virus showing icosahedral symmetry.

Nucleocapsid of a helical virus

Nucleic acid + capsid → nucleocapsid.

GENERAL STRUCTURE OF AN ENVELOPED VIRUS.

[Nucleic acid + capsid] + envelope with glycoproteins (peplomers)

Principles of virus structure. Virion

is

the complete extracellular virus particle.

STRUCTURE

I.

Capsid is a protein shell.

Symmetry of capsid. 2.Helical Repeated

units of a single polypeptide (protomer) Protein subunits are in association with the viral nucleic acid Self-assemble into a helical cylinder (rod-shaped)

1. Icosahedral (cubic).  More complex, with several

different polypeptides  Polypeptides grouped into identical capsomers and form an icosahedron (20 faces, 12 vertices).  Nucleic acid genome is located within the empty space.

Functions: Protection of the viral genome  Site of receptors necessary for naked viruses to initiate infection  Stimules for antibody production  Site of antigenic determinants, important in some serologic tests. 

I.

Genome is a type of viral nucleic acid. RNA or DNA (either may be singlestrainded (ss) or double-strainded (ds)). Positive-sense RNA genome Negative-sense RNA genome Non-segmented RNA genome (linear) Segmented RNA genome Linear configuration DNA Circular configuration DNA

I. Envelope Lipid-containing membrane surrounding the nucleocapsid Derived from host cell membranes Contain virus-specific glycoproteins (peplomers).

Properties have been used as a Basis for the classification of viruses. Virion morphology (size, shape, type of symmetry, presence or absence of peplomers, presence or absence of membranes). 2. Physicochemical properties of the virion (molecular mass, PH stability, thermal stability, susceptibility to physical and chemical agents). 1.

Virus genome properties (type of NA, size of genome; strandedness: single or double, sence: positive, negative, ambisense; linear or circular; segments…) Genome organization and replication Virus protein properties (structural, nonstructural, modifications). Antigenic properties. Biologic properties (natural host, mode of transmission, tissue tropisms).

Main determinants for dividing viruses into families.

Genome structure Virion structure Strategies of replication

Main determinants for dividing viruses into genera and species. Physicochemical differences Serologic differences Degree of NA homology Host range Tissue specificity

Examples of the CLASSIFICATION of VIRUSES UNIVERSAL SYSTEM of VIRUS TAXONOMY Family (″- viridae") Sub-family (″-virinae") Genera (″-virus") Species Strains

Examples of the Classification of viruses: I. DNA viruses 2. Herpesviridae 3. Alpha-herpesvirinae (herpes simplex group) Herpes simplex 1 Herpes simplex 2 Varicella- zoster virus

1.

5.

Beta-herpesvirinae (cytomegalovirus group) Human cytomegalovirus Human herpesvirus 6 Human herpesvirus 7 Gamma-herpesvirinae (lymphoproliferative group) Epstein-Barr virus Human herpesvirus 8

I.

RNA viruses

Picornaviridae 3. Enterovirus Coxsackie virus Echovirus Poliovirus 7. Rhinovirus 8. Hepatovirus Hepatitis A virus 2.

Viral replication

Steps in the replication cycles of viruses 1. 

Adsorption Attachment of a virion to a specific host cell receptor

1. Penetration (taken up inside the cell)



By receptormediated endocytosis

By

membrane fusion (direct penetration)

1.

Uncoating Separation of the viral genome from the outer structural components of the virion such that it can function.

3.

Macromolecular synthesis of viral components

Genome replication  Transcription  Translation 

•

6.

Assembly and maturation of the virus

Release of virus  Lysis (disintegration of the cell)  Budding – process by which enveloped viruses obtain their envelope.

Mechanism of DNA virus genome replication

Mechanism of RNA virus genome replication Type I: viruses with an ssRNA genome of (+) polarity that replicates via a complementar y (-) strand intermediate

Type II: viruses with a ssRNA genome of (-) polarity that replicates via a complementary (+) strand intermediate

Type III: Viruses with a dsRNA genome

ype IV: Viruses with a genome of ssRNA of (+) polarity that is replicated via a DNA intermediate

Effects of viral infection on a host cell. Abortive

infection - a normal virus in nonpermissive cell, defective virus in normal cell. Persistent infection - (the host cell may be altered antigenically). Persistance of the viral genome.

Latent infectiontumor viruses Herpes virus In some cases cause cell transformation Lytic, productive infection (cytocidal virus)

Effects of viral infection on a host cell.