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VIROLOGY - LECTURE ONE 

  BASIC VIROLOGY: DEFINITIONS, CLASSIFICATION, 
MORPHOLOGY AND CHEMISTRY  

Dr. Margaret Hunt

MEDICAL MICROBIOLOGY, MBIM 650/720 LECTURES 49/50

Click thumbnails to enlarge images

Reading: Murray et al., Microbiology, 3rd Ed., Chapter 6

Virus structure and replication are fundamentally different from those of cellular 
organisms. 

 «The arenavirus family (an RNA virus family) appears to package ribosomes
 'accidentally', the packaged ribosomes appear to play no role in viral protein 
 synthesis.

Relative sizes of viruses
Relative size of viruses and bacteria      Adapted from  Koneman et al. Color Atlas and Textbook of Microbiology 5th Ed. 1997 Virus images © Dr Linda Stannard, University of Cape Town. Used with permission	Relative size of DNA viruses  Images © 1995  Dr Linda Stannard, University of Cape Town and © 1994 Veterinary Sciences Division, Queen's University Belfast
Relative size of positive strand RNA viruses  Images © 1995  Dr Linda Stannard, University of Cape Town and © 1994 Veterinary Sciences Division, Queen's University Belfast	Relative size of negative strand RNA viruses Images © 1995  Dr Linda Stannard, University of Cape Town and © 1994 Veterinary Sciences Division, Queen's University Belfast

NOTE: Viral dependence on the host cell for various aspects of the growth cycle
has complicated the development of drugs which inhibit viral multiplication but not 
cell growth. It is advantageous to know when the virus provides its own enzymes 
for part of its replication cycle - we can then try to develop drugs which inhibit the 
viral enzymes specifically.

Viruses infect all major groups of organisms: vertebrates, invertebrates, 
plants, fungi, bacteria.

Some viruses have a broader host range than others, but none can cross 
the eukaryotic/prokaryotic boundary.

Factors which affect host range include:

i) whether the virus can get into the host cell

ii) if the virus can enter the cell, is the appropriate cellular machinery available for the virus to replicate?

iii) if the virus can replicate, can infectious virus get out of the cell and spread the infection?

 

Viruses contain:

a nucleic acid genome (RNA or DNA)

a protective protein coat (called the capsid)

The nucleic acid genome plus the protective protein coat = nucleocapsid

The nucleocapsid may have icosahedral or helical symmetry

Viruses may or may not have an envelope made of lipid derived from the host cell

Enveloped viruses obtain their envelope by budding through a host cell 
membrane. In some cases, the virus buds through the plasma membrane 
but in other cases the envelope may be derived from other membranes 
such as those of the Golgi body or the nucleus.

The envelope consists of a lipid bilayer and proteins and always includes 
at least one virally coded protein involved in attachment.

Enveloped viruses do not necessarily have to kill cell in order to be 
released, since they can bud out of the cell - a process which is not 
necessarily lethal to the cell - hence some budding viruses can set up 
persistent infections.

Enveloped viruses are readily infectious only if the envelope is intact (since the
 viral attachment proteins which recognize the host cell receptors are in the viral 
envelope if it is an enveloped virus). So agents which damage the envelope 
reduce infectivity.

A) ICOSAHEDRAL

Icosahedron: solid figure, 20 faces, 5:3:2 rotational symmetry

12 corners or vertices, 5-fold symmetry around vertices

  Icosahedral symmetry in viruses

The capsid shell is made of repeating subunits of viral protein (may be one kind 
of subunit or several, according to the virus).

All faces of the icosahedron are identical.

The nucleic acid is packaged inside the capsid shell and protected from the 
environment by the capsid.

Proteins associate into structural units (this is what one sees in the electron 
microscope or when start to disassociate a capsid), the structural units are known 
as capsomers - capsomers may contain one or several kinds of polypeptide 
chain.

Capsids with icosahedral symmetry have 12 vertices, capsomers at the 12 corners 
have a 5-fold symmetry and interact with 5 neighboring capsomers, and are thus 
known as pentons (or pentamers).

Adenovirus symmetry

Components of an icosahedral capsid

Human adenovirus seen by negative staining © 1995  Dr Linda Stannard, University of Cape Town. Used with permision

Larger viruses contain more capsomers, extra capsomers are arranged in a 
regular array on the  faces of the icosahedrons, these often have six neighbors 
and are called hexons (or hexamers).

The size of such an icosahedron depends on the size and number of capsomers, 
there will always be 12 pentons, but the number of hexons may increase.

B) HELICAL

Protein subunits interact with each other and with the nucleic acid to form a coiled, 
ribbon like structure:

e. g. tobacco mosaic virus, influenza virus, rabies virus

Close up of tobacco mosaic virus rods © 1994 Rothamsted Experimental Station	Tobacco Mosaic Virus  (TEM x376,200)  © Dr Dennis Kunkel, University of Hawaii. Used with permission
Close up of a single TMV rod. Image from the International Committee on Taxonomy of Viruses database.	Tobacco Mosaic Virus  (TEM x207,480)   © Dr Dennis Kunkel, University of Hawaii. Used with permission
Rabies virus  Wadsworth Center, NY Dept of Health	Influenza Virus © 1995  Dr Linda Stannard, University of Cape Town. Used with permision

Tobacco mosaic virus structure showing a helical capsid structure

Helix may be very rod-like and inflexible (tobacco mosaic virus) or very flexible 
(Paramyxoviruses).

C) COMPLEX
Regular structures, but nature of symmetry not fully understood. Example: poxviruses

Complex symmetry found in poxviruses Fenner and White Medical Virology 4th Ed. 1994

Pox virus seen by negative staining © Stewart McNulty, 1994 Veterinary Sciences Division, Queen's University Belfast

FIVE BASIC STRUCTURAL FORMS OF VIRUSES IN NATURE

1. naked icosahedral

e.g. poliovirus, adenovirus, hepatitis A virus

e.g. tobacco mosaic virus, so far no human viruses with this structure known

3. enveloped icosahedral

e.g. herpes virus, yellow fever virus, rubella virus

4. enveloped helical

e.g. rabies virus, influenza virus, parainfluenza virus, mumps virus, measles virus

5. complex

e.g. poxvirus

Five basic types of virus symmetry

There are also the 'unconventional agents' sometimes known as 'unconventional 
viruses' or 'atypical viruses' - the main kinds which have been studied so far are:

VIROIDS

Viroids contain RNA only. Small (less than 400 nucleotides), single stranded, 
circular RNAs, these are not packaged, do not appear to code for any proteins, 
and so far have only been shown to be associated with plant disease. However, 
there are some suggestions that somewhat similar agents may possibly be 
involved in some human disease.

So far the only known human disease agent to resemble viroids is hepatitis delta 
agent. This agent has a small RNA genome, although somewhat larger than the 
true viroids, but features of the nucleic acid sequence and structure are somewhat 
similar to viroids. Hepatitis delta agent (also known as hepatitis delta virus) does 
not code for its own attachment protein, but unlike the viroids, it is packaged - it 
acts as a parasite on hepatitis B virus, and uses hepatitis B virus envelopes with 
the hepatitis B attachment protein. Hepatitis delta agent differs from viroids in that 
it does code for a few proteins. In some ways hepatitis delta agent appears to be 
intermediate between 'classical viruses' and viroids.

PRIONS

Prions contain protein only (although this is somewhat controversial). They are 
small, proteinaceous particles and there is controversy as to whether they contain 
any nucleic acid, but if there is any, there is very little, and almost certainly not 
enough to code for protein: e.g. scrapie, Kuru, Creutzfeldt-Jakob disease, 
Gerstmann-Straussler syndrome

This depends on the definition of life. To avoid possible arguments, we often 
refer to whether they have or have lost some aspect of their biological activities 
rather than referring to living or dead viruses. (Hence we talk about number of 
infectious particles,or number of plaque forming particles rather than number 
of living particles.)

The internationally agreed system is based on structure/composition of the virus 
particle (virion), in some cases, the mode of replication is also important. Viruses 
are classified into various families on this basis.

Some alternative classifications are/were also used (e.g. arboviruses, 
which include various members of various families which are arthropod 
borne).

 

Replication strategy

Sometimes a group of viruses which seems to be a single group 
by the above criteria is found to contain a subgroup of viruses which 
have a fundamentally different replication strategy - in this case the 
group will be divided based on the mode of replication.

Families of DNA viruses

Families of RNA viruses

GLOSSARY

CAPSID   The protein coat that surrounds the nucleic acid of a virus.

CAPSOMERS   Substructures of virus particles. Composed of aggregates of 
polypeptide chains that interact to form the basic structural units of the capsid.

CASE FATALITY RATE (=CFR)   The proportion of clinically apparent cases 
which result in death.

CYTOPATHIC EFFECT (=CPE)   CPE consists of morphologic alterations of host 
cells, may result in cell death.

ENVELOPE   A host-cell-derived membrane, containing virus specific antigens, 
that  is acquired during virus maturation.

FOMITE   An object (e.g. furniture, book) that is not harmful in itself but which can 
harbor pathogenic organisms and thus may be involved in transmission of an 
infection

GENOME   A set of genes.

GIANT CELLS   See SYNCYTIUM.

HEMADSORPTION   The attachment of red blood cells to the surface of host cells.

HEMAGGLUTINATION    Aggregation of red blood cells.

ICOSAHEDRON   A geometric figure composed of 12 vertices, 20 triangular faces 
and 30 edges.

INCLUSION BODIES   Usually sites of virus synthesis or assembly; may be of 
diagnostic value (e.g. Negri bodies in rabies infection).

NANOMETER   10^-9meter. 1nm = 10Å. 1000nm = 1µm.

NUCLEOCAPSID   The virus structure composed of the nucleic acid surrounded 
by the capsid.

MONOLAYER   Sheet of cells forming a continuous layer one cell thick on a solid 
(e.g.glass or plastic) surface. Cells may be e.g. fibroblast, epithelial, epitheliod in 
nature. They may exist in either primary or continuous (transformed) state.

PEPLOMERS   See SPIKES (peplos = envelope).

PLAQUE   A defined area of cell destruction resulting from virus infection in vitro.

PLAQUE FORMING UNIT (=PFU)   A measure of infectious virus particles. 
One plaque forming unit is equivalent to one infectious virus particle.

POCK   A discrete pustular lesion found in the chorioallantoic membrane or skin 
following infection with certain viruses.

SPIKES   Surface projection of varying lengths spaced at regular intervals on the 
viral envelope, also called peplomers. Consist of viral glycoproteins

STRUCTURAL PROTEINS   Those proteins which are present in the virion. THIS 
INCLUDES PROTEINS PRESENT IN LOW AMOUNTS. 'STRUCTURAL PROTEINS' 
do NOT necessarily play a skeletal role in maintaining a virus's shape.

SYNCYTIUM   A multinucleated protoplasmic mass formed by the fusion of 
originally separate cells

VIRAL HEMAGGLUTININ   A virally coded protein on the outer surface of some 
viruses which reacts with a surface determinant on red cells. Since such a virion 
will have many copies of the surface hemagglutinin, it can bind to more than one 
red blood cell, thus causing hemagglutination.

VIRAL INFECTIOUS DOSE    The amount of virus required to cause a 
demonstrable infection in 50% of the inoculated animals (ID₅₀) or tissue culture 
cells (TCID₅₀).

VIREMIA   Presence of virus particles in the blood

VIRION    The mature virus particle, with all of its structural components intact.

VIRUS    A small, obligate intracellular parasite that depends on a living host cell 
for energy, precursors, enzymes, and ribosomes to multiply. It consists of a single 
type of nucleic acid, either DNA or RNA, and a protein coat surrounding the 
nucleic acid. In addition, some viruses have an envelope. 

I = ICOSAHEDRAL SYMMETRY, H = HELICAL SYMMETRY, C = COMPLEX SYMMETRY

ABOVE DNA VIRUS FAMILIES ARE LISTED IN ORDER OF INCREASING GENOME SIZE