Virology: Definition, Classification, Morphology,& Struc

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Viruses consist of a nucleic acid (either DNA or RNA) associated with proteins encoded by the nucleic acid. The virus may also have a lipid bilayer membrane (or envelope) but this is acquired from the host cell, usually by budding through a host cell membrane. If a membrane is present, it must contain one or more viral proteins to act as ligands for receptors on the host cell. Many viruses encode a few structural proteins (those that make up the mature virus particle (or virion)) and perhaps an enzyme that participates in the replication of the viral genome. Other viruses can encode many more proteins, most of which do not end up in the mature virus but participate in some way in viral replication. Herpes virus is one of the more complicated viruses and has 90 genes. Since many viruses make few or no enzymes, they are dependent on host cell enzymes to produce more virus particles. Thus virus structure and replication are fundamentally different from those of cellular organisms. Viral dependence on the host cell for various aspects of the growth cycle has complicated the development of drugs since most drugs will inhibit cell growth as well as viral multiplication (because the same cell enzymes are used). Since a major reason to study viral metabolism is to find drugs that selectively inhibit the multiplication of viruses, we need to know when the virus uses its own proteins for part of its replication cycle - we can then try to develop drugs which inhibit the viral proteins (especially viral enzymes) specifically. In contrast to viruses, the much larger bacteria (figure 1) carry out their own metabolic processes and code for their own enzymes. Even when catalyzing similar reactions, bacterial enzymes differ from their eukaryotic homologs and can therefore be targeted by specific antibiotics. Like viruses, some bacteria (such as mycoplasma, rickettsia and chlamydia) can enter the cytoplasm of eukaryotic cells and become parasites. These small intracellular bacteria nevertheless provide all of the enzymes that are necessary for replication. Thus, mechanisms for control of bacteria, including those with a parasitic lifestyle, are more easily developed than for viruses.

Viruses infect all major groups of organisms: vertebrates, invertebrates, plants, fungi, bacteria but some viruses have a broader host range than others; however, 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?

VIRUS STRUCTURE

Viruses range in size from less than 100 nanometers in diameter to several hundred nanometers in length in the case of the filoviridae.

All viruses contain a nucleic acid genome (RNA or DNA) and a protective protein coat (called the capsid). The nucleic acid genome plus the protective protein coat is called the nucleocapsid which may have icosahedral, helical or complex symmetry. Viruses may or may not have an envelope. 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. Some viruses bud through specialized parts of the plasma membrane of the host cell; for example, Ebola virus associates with lipid rafts that are rich in sphingomyelin, cholesterol and glypiated proteins. Poxviruses are exceptional in that they wrap themselves in host cell membranes using a mechanism that is different from the usual budding process used by other viruses.

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, such as alcohols and detergents, reduce infectivity.

VIRION NUCLEOCAPSID STRUCTURES

A) Icosahedral symmetry

An icosahedron is a Platonic solid with twenty faces and 5:3:2 rotational symmetry. There are six five-fold axes of symmetry through which the icosahedron can be rotated passing through the vertices, ten 3-fold axes of symmetry passing though each face and fifteen two-fold axes of symmetry passing through the edges. There are twelve corners or vertices and 5-fold symmetry around vertices. The capsid shell is made of repeating subunits of viral protein (There 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 we see in the electron microscope or when we start to disassociate a capsid), the structural units are known as capsomers - capsomers may contain one or several kinds of polypeptide chain. Capsomers at the 12 corners have a 5-fold symmetry and interact with 5 neighboring capsomers, and are thus known as pentons or pentamers. Larger viruses contain more capsomers; extra capsomers are arranged in a regular array on the faces of the icosahedrons. They have six neighbors and are called hexons or hexamers.

The size of an icosahedron depends on the size and number of capsomers; there will always be 12 pentons (at each corner) but the number of hexons increases with size. A good example of an icosahedral virus is human adenovirus which contains the usual twelve pentons plus two hundred and forty hexons. The symmetrical formation of hexagonal arrays on a flat face occurs in many situations; for example, in the packing of test tubes in a box. It can also be seen in the packing of the subunits of herpes virus, an enveloped icosahedral virus. Although icosahedrons are flat-faced, viral icosahedrons are usually round as seen in figure 3K. A good example of a small round icosahedron is a normal soccer ball. A larger icosahedron is a geodesic dome.

B) Helical symmetry

Protein subunits can interact with each other and with the nucleic acid to form a coiled, ribbon like structure. The best studied virus with helical symmetry is the non-enveloped plant virus tobacco mosaic virus. The helical nature of this virus is quite clear in negative staining electron micrographs since the virus forms a rigid rod-like structure. In enveloped helically symmetrical viruses (e. g. influenza virus, rabies virus), the capsid is more flexible (and longer) and appears in negative stains rather like a telephone cord.

C) Complex symmetry

These are regular structures, but the nature of the symmetry is not fully understood. Examples include the poxviruses.

FIVE BASIC STRUCTURAL FORMS OF VIRUSES IN NATURE

Naked icosahedral e.g. poliovirus, adenovirus, hepatitis A virus

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

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

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

Complex e.g. poxvirus

UNCONVENTIONAL AGENTS

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 and prions.

VIROIDS

Viroids contain RNA only. They are small (less than 400 nucleotides), single stranded, circular RNAs. The RNAs 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 diseases.

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

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: Examples of prion-caused human diseases are Kuru, Creutzfeldt-Jakob disease and Gerstmann-Straussler syndrome. Prions also cause scrapie in sheep.

ARE VIRUSES LIVING OR DEAD?

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.)

CLASSIFICATION OF VIRUSES

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

INTERNATIONAL CLASSIFICATION OF VIRUSES

Primary characteristics used in classification

Viruses are classified according to the nature of their genome and their structure

Nucleic acid------------------- RNA or DNA
single-stranded or double-stranded
non-segmented or segmented
linear or circular
if genome is single stranded RNA, can it function as mRNA?
whether genome is diploid (it is in retroviruses)
Virion structure------------------ symmetry (icosahedral, helical, complex)
enveloped or not
number of capsomers

Secondary characteristics

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.

DNA VIRUSES

PARVOVIRIDAE
I
-
20nm

Include adeno-associated virus, human parvovirus B19.

HEPADNAVIRIDAE
I
+
42nm
+
DNA replicates via an RNA intermediate. Includes hepatitis B virus which may increase risk of hepatocarcinoma.

PAPILLOMA-
VIRIDAE * I
-
40-60nm
-
some members cause warts, some associated with increased risk of cervical cancer
POLYOMA-VIRIDAE *
I
-
40-60nm
-
SV40, some members cause PML.

ADENOVIRIDAE
I
-
80nm
-
More than 40 human serotypes

HERPESVIRIDAE
I
+
190nm
-
Latency common. Includes herpes simplex type 1 and 2, varicella zoster virus (chicken pox, shingles), Epstein Barr virus (infectious mononucleosis), cytomegalovirus.

POXVIRIDAE
C
+
200nm x 350nm
+
Vaccinia, smallpox, cowpox viruses Cytoplasmic, very complex.

* Formerly grouped together as the PAPOVAVIRIDAE

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

RNA VIRUSES - POSITIVE SENSE

PICORNAVIRIDAE
I
-
30nm
-
Includes enteroviruses, rhinoviruses, coxsackie virus, poliovirus, hepatitis A virus

CALICIVIRIDAE
I
-
35nm
-
gastroenteritis, Norwalk agent probably a member

TOGAVIRIDAE
I
+
60-70nm
-
Alphavirus genus: includes western equine encephalitis virus (WEE), eastern equine encephalitis virus (EEE),Venezuelan equine encephalitis virus, Chikungunya virus, Sindbis virus, Semliki Forest virus Rubrivirus genus: contains only rubella virus

FLAVIVIRIDAE
I
+
40-55nm
-
Include yellow fever, dengue, Japanese encephalitis, St. Louis encephalitis viruses, etc. Have only recently been given family status (formerly classed with Togaviridae).

CORONAVIRIDAE
H
+
75-160nm
-
Estimated responsible for 10-30% of common colds

RETROVIRIDAE
I
+
100nm
+
Have reverse transcriptase, some members oncogenic in animals. HIV is a member. Diploid genome.

RNA VIRUSES - NEGATIVE SENSE

RHABDOVIRIDAE

H
+
60 x 180nm
+
These include rabies virus, vesicular stomatitis virus, Mokola virus, Duvenhage virus

PARAMYXOVIRIDAE
H
+
150-300nm
+
Includes Newcastle disease virus, parainfluenza viruses, mumps virus, measles virus, respiratory syncytial virus

ORTHOMYXOVIRIDAE
H
+
80-120nm
+
Influenza type A and B viruses have segmented genome. They steal mRNA caps

BUNYAVIRIDAE
H
+
95nm
+
Over 86 members, most have arthropod vectors. Members include California encephalitis, LaCrosse, Crimean-Congo hemorrhagic fever, and Rift Valley fever viruses. Members of the hantavirus genus (includes agents of Korean hemorrhagic fever, human pulmonary syndrome in britain) seem to have rodent vectors. Segmented genome.

ARENAVIRIDAE
H
+
50-300nm
+
Includes lymphocytic choriomeningitis, Lassa, Junin (Argentine hemorrhagic fever), and Machupo (Bolivian hemorrhagic fever) viruses. Segmented genome

FILOVIRIDAE
H
+
80nm x 800-900nm
+
Marburg virus, Ebola virus, Reston virus

RNA VIRUSES - DOUBLE STRANDED

REOVIRIDAE
I
-
75nm
+
The reoviridae include the reovirus, rotavirus and orbivirus genera.

Human reovirus infections are apparently asymptomatic.,

Members of this group that affect humans include Colorado tick fever virus (orbivirus) and human rotaviruses (can cause gastroenteritis). All of these viruses have segmented genomes.