Microbiology and Immunology

WORLD OF MICROBIOLOGY AND IMMUNOLOGY Virology, viral classification, types of viruses

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The use of virusesquickly became an attractive possi-

bility once the possibility of gene therapy became apparent.

Viruses require other cells for their replication. Indeed, an

essential feature of a virus replicationcycle is the transfer of

their genetic material (deoxyribonucleic acid, DNA; or ribonu-

cleic acid, RNA) into the host cell, and the replication of that

material in the host cell. By incorporating other DNA or RNA

into the virus genome, the virus then becomes a vector for the

transmission of that additional genetic material. Finally, if the

inserted genetic material is the same as a sequence in the host

cell that is defective, then the expression of the inserted gene

will provide the product that the defective host genome does

not. As a result, host defective host genetic function and the

consequences of the defects can be reduced or corrected.

Retrovirusescontain RNA as the genetic material. A

viral enzyme called reverse transcriptase functions to manu-

facture DNA from the RNA, and the DNA can then become

incorporated into the host DNA. Despite the known involve-

ment of some retroviruses in cancer, these viruses are attrac-

tive for gene therapy because of their pronounced tendency to

integrate the viral DNA into the host genome. Retroviruses

used as gene vectors also have had the potential cancer-caus-

ing genetic information deleted. The most common retrovirus

that has been used in experimental gene therapy is the

Moloney murine leukaemia virus. This virus can infect cells of

both mice and humans. This makes the results obtained from

mouse studies more relevant to humans.

Adenovirusesare another potential gene vector. Once

they have infected the host cell, many rounds of DNA replica-

tion can occur. This is advantageous, as much of the therapeu-

tic product could be produced. However, because integration

of the virally transported gene does not occur, the expression

of the gene only occurs for a relatively short time. To produce

levels of the gene product that would have a substantial effect

on a patient, the virus vector needs to administered repeatedly.

As for retroviruses, the adenoviruses used as vectors need to

be crippled so as to prevent the production of new viruses.

Adenovirus vector has been used to correct mutations

the gene that is defective in cystic fibrosis. However, as of

May 2002, the success rate in human trials remained low. In

addition, the immune response to the high levels of the vector

that are needed can be problematic.

Another important aspect of gene therapy concerns the

target of the viral vectors. The viruses need to be targeted at

host cells that are actively dividing, because only in cells in

which DNA replication is occurring will the inserted viral

genetic material be replicated. This is one reason why cancers

are a conceptually attractive target of virus-mediated gene

therapy, as cancerous cells are dangerous by virtue of their

rapid and uncontrolled division.

Cancerous cells arise by some form of mutation.

Therefore, therapy to replace defective genes with functional

genes holds promise for cancer researchers. The target of gene

therapy can vary, as many cancers have mutations that direct a

normal cell towards acquiring the potential to become cancer-

ous, and other mutations that inactivate mechanisms that func-

tion to regulate growth control. Furthermore, gene therapy can

be directed at the immune systemrather than directly at the

cancerous cell. An example of this strategy is known as

immunopotentiation (the enhancement of the immune

response to cancers).

A risk of viral gene therapy, in those viruses that oper-

ate by integrating genetic material into the host genome, is the

possibility of damage to the host DNA by the insertion.

Alteration of some other host gene could have unforeseen and

undesirable side effects. The elimination of this possibility

will require further technical refinements. Adenoviruses are

advantageous in this regard as the replication of their DNA in

the host cell does not involve insertion of the viral DNA into

the host DNA. Accordingly, the possibility of mutations due to

insertion do not exist.

The September 1999 death of an 18 year old patient

with a rare metabolic condition, who died while receiving

viral gene therapy, considerably slowed progress on clinical

applications of viral gene therapy.

See alsoBiotechnology

VIROLOGY, VIRAL CLASSIFICATION,

TYPES OF VIRUSESVirology, viral classification, types of viruses

Virology is the discipline of microbiology that is concerned

with the study of viruses. Viruses are essentially nonliving

repositories of nucleic acid that require the presence of a liv-

ing prokaryotic or eukaryotic cell for the replication of the

nucleic acid.

Scientists who make virology their field of study are

known as virologists. Not all virologists study the same things,

as viruses can exist in a variety of hosts. Viruses can infect ani-

mals (including humans), plants, fungi, birds, aquatic organ-

isms, protozoa, bacteria, and insects. Some viruses are able to

infect several of these hosts, while other viruses are exclusive

to one host.

All viruses share the need for a host in order to replicate

their deoxyribonucleic acid(DNA) or ribonucleic acid(RNA).

The virus commandeers the host’s existing molecules for the

nucleic acid replication process. There are a number of differ-

ent viruses. The differences include the disease symptoms

they cause, their antigenic composition, type of nucleic acid

residing in the virus particle, the way the nucleic acid is

arranged, the shape of the virus, and the fate of the replicated

DNA. These differences are used to classify the viruses and

have often been the basis on which the various types of viruses

were named.

The classification of viruses operates by use of the same

structure that governs the classification of bacteria. The

International Committee on Taxonomy of Viruses established

the viral classification scheme in 1966. From the broadest to

the narrowest level of classification, the viral scheme is:

Order, Family, Subfamily, Genus, Species, and Strain/type. To

use an example, the virus that was responsible for an outbreak

of Ebola hemorrhagic fever in a region of Africa called Kikwit

is classified as Order Mononegavirales, Family Filoviridae,

Genus Filovirus, and Species Ebola virusZaire.

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