General Virology

Dr. Kiani
Assistant Professor
Department of Virology, School of Medicine
Iran University of Medical Sciences
Reference

2
 What is Virus?

 The smallest infectious agents (ranging from about 20 to 300 nm in diameter)

 Genome: only one kind of nucleic acid (RNA or DNA)

 A protein coat

 With/without lipid-containing membrane

 Parasites at the genetic level (replicating only in living cells)

 Inert in the extracellular environment

 Viroids and Prions

3
 Terminology
 Capsid: the protein shell, or coat, that encloses the nucleic
acid genome.

 Capsomeres: morphologic units seen in the electron

microscope on the surface of icosahedral virus particles.

 Peplomers: virus glycoproteins

 Envelope: a lipid-containing membrane that surrounds

some virus particles.

 Nucleocapsid: the protein–nucleic acid complex

representing the packaged form of the viral genome.
4
 Virion: the complete virus particle (entire infectious unit)
Classification of Viruses

5
6
 Principles of Virus Structure

Genetic economy requires that a viral structure be made from many

identical molecules of one or a few proteins.

Viral architecture (based on the arrangement of morphologic subunits):

(1) Cubic symmetry

(2) Helical symmetry

(3) Complex structures

7
 A. Cubic Symmetry

 Icosahedral pattern:

 60 (or 60x) identical subunits

 20 faces

 12 vertices

 Symmetry axes: 2-, 3-, and 5-fold

 Units in Vertex: five neighbors (pentavalent)

 Unites in Faces: six neighbors (hexavalent)

8
 B. Helical Symmetry

 Protein subunits bound to the viral nucleic acid, winding

it into a helix.

 A regular, periodic interaction between capsid protein

and nucleic acid (unlike icosahedrons)

 “EMPTY” helical particles: not possible

 All known examples: contain RNA genomes

9
 C. COMPLEX STRUCTURES

 Some virus particles do not exhibit simple cubic or helical symmetry

 More complicated structures
 Poxviruses:
• brick shaped
• ridges on the external surface
• a core
• lateral bodies
10
 Chemical Composition of Viruses
Proteins
Structural Proteins:

Attachment of the virus particle to a susceptible cell

Protect the viral genome against inactivation by nucleases

Facilitate transfer of the viral nucleic acid from one host cell to another

Specific activities (HA, RNA polymerase, reverse transcriptase)

Non-structural Proteins:

 Enhancement of virus replication in the host cell/organism

11
 Chemical Composition of Viruses
Nucleic Acid

 Type: DNA or RNA

 Size: 1.7 kbp (Circoviridae) to 375 kbp (poxviruses)
 Strandedness: single or double
 Shape: circular or linear
 Segmentation: segmented or non-segmented
 Sense: positive-, negative-, or ambi-sense
• positive-sense RNA is infectious (functions as mRNA)
• negative-sense RNA is not infectious (virions carry an RNA polymerase)
12
 Chemical Composition of Viruses
Envelopes

 Some viruses contain lipid envelopes

 Acquired when the viral nucleocapsid buds through a cellular

membrane

 Enveloped viruses: sensitive to treatment with ether and other organic

solvents

 Non-enveloped viruses: generally resistant to ether and detergents

13
 Cultivation and Detection
of Viruses
 Cultivation of Viruses:
• Cell cultures
• Fertile eggs
• Animals
 Three basic types of cell cultures:
• Primary cultures from freshly removed host tissues (a few passages)
• Diploid cell lines: undergone a change for limited culture (up to 50
passages) with normal chromosome pattern
• Continuous cell lines: capable of more prolonged culture (perhaps
indefinite) with altered numbers of chromosomes 14
Detection of Virus-infected Cells
1. Cytopathic effects: cell lysis or necrosis, inclusion body formation,
giant cell formation, and cytoplasmic vacuolization
2. Appearance of a virus-encoded protein: hemagglutinin of influenza
virus
3. Detection of virus-specific nucleic acid
4. Hemadsorption: adsorption of erythrocytes to cell membrane of the
infected cells
5. Embryonated egg: death of the embryo (eg, encephalitis viruses),
production of pocks or plaques on the chorioallantoic membrane
(eg, herpes, smallpox, vaccinia), or development of hemagglutinins
in the embryonic fluids or tissues (eg, influenza).
15
 Reaction to Physical and
Chemical Agents
Heat
 37 ℃:
 Icosahedral viruses tend to be stable
 Enveloped viruses are much more heat labile
 50–60 ℃ (for 30 minutes):
 generally destroyed (exceptions: hepatitis B virus, polyomaviruses)
Cold
 preserved at subfreezing temperatures, and some may withstand lyophilization.
 Enveloped viruses tend to lose infectivity after prolonged storage even at −90 ℃
(sensitive to repeated freezing and thawing) 16
 Reaction to Physical and
Chemical Agents
Stabilization by salts
 to resist heat inactivation: preparation of vaccines (MgCl2 for polio vaccine)
pH
 usually stable between pH values of 5.0 and 9.0
 Some viruses are resistant to acidic conditions
 All viruses are destroyed by alkaline conditions
Radiation
 Ultraviolet, X-ray, and high-energy particles inactivate viruses
 Infectivity is the most radiosensitive property 17
 Reaction to Physical and
Chemical Agents

Ether susceptibility
 To distinguish between enveloped and non-enveloped viruses

Formaldehyde
 Destroys viral infectivity by reacting with nucleic acid.
 Minimal adverse effects on the antigenicity of proteins (production of inactivated
viral vaccines)

18
 Replication of Viruses

 Productive infection: in permissive cells results in the production of infectious virus

 Abortive infection: fail to produce infectious progeny (nonpermissive cell or and

defective virus)

 Latent infection: persistence of viral genomes, the expression of no or a few viral

genes, and the survival of the infected cell.

19
 Replication of Viruses

Viruses multiply only in living cells

Host cell provides the energy, material, and synthetic machinery

Eclipse period: soon after interaction with a host cell the

infecting virion is disrupted and its measurable infectivity is lost.
20
 General Steps in Viral Replication Cycles
1) Attachment
• Interaction with a specific receptor on the surface of a cell
• presence or absence of receptors: cell tropism and viral pathogenesis
2) Penetration:
• receptor-mediated endocytosis
• direct penetration
• fusion of the virion envelope with the plasma membrane
3) Uncoating
• physical separation of the viral nucleic acid from the outer structural components of the virion
• Releases free nucleic acid or nucleocapsid
• Uncoating may require acidic pH in the endosome
21
• The infectivity of the parental virus is lost at the uncoating stage
22
 Replication of the genome

DNA viruses:
 in the nucleus (exception: Poxviruses)
 with cellular DNA polymerases (exceptions: Adeno, Herpes,
Pox, Hepadna)
RNA viruses:
 in the cytoplasm (exceptions: Retro, Orthomyxo, Borna, Delta)
 with viral RNA polymerases (exceptions: Retro, Delta)

23
24
 Morphogenesis and Release

 Newly synthesized viral genomes and capsid polypeptides assemble to

form progeny viruses.

 Non-enveloped viruses accumulate in infected cell, lyse it and release.

 Enveloped viruses mature by a budding process from cellular membranes

 Some instances: cell is not damaged by the virus and long-term, persistent
infections evolve.

25
 Modes of Transmission

1. Direct transmission by contact:

 droplet or aerosol infection (eg, influenza, rhinovirus, measles, smallpox)
 sexual contact (eg, papillomavirus, hepatitis B, herpes simplex type 2, HIV)
 hand–mouth, hand–eye, or mouth–mouth contact (eg, herpes simplex, epstein-barr virus)
 exchange of contaminated blood (eg, hepatitis B, hepatitis C, HIV)

26
 Modes of Transmission

2. Indirect transmission:
 fecal–oral route (eg, enteroviruses, rotaviruses, hepatitis A)
 fomites (eg, norwalk virus, rhinovirus)
3. Transmission from animal to animal (with humans as accidental host):
 bite (rabies)
 droplet or aerosol (eg, arenaviruses, hantaviruses)
4. Transmission by means of an arthropod vector (eg, arboviruses)

27
Thank you
28