Microbiology and Immunology

WORLD OF MICROBIOLOGY AND IMMUNOLOGY Virus replication

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manufacture the RNA that is eventually packaged into the new

virus particles. The main example is the Retroviruses(the

Human ImmunodeficiencyViruses belong here). Finally, a

group of viruses consist of double-stranded DNA that is used

to produce a RNA intermediate. An example is the

Hepadnaviruses.

An aspect of virology is the identification of viruses.

Often, the diagnosis of a viral illness relies, at least initially, on

the visual detection of the virus. For this analysis, samples are

prepared for electron microscopy using a technique called

negative staining, which highlights surface detail of the virus

particles. For this analysis, the shape of the virus is an impor-

tant feature.

A particular virus will have a particular shape. For

example, viruses that specifically infect bacteria, the so-called

bacteriophages, look similar to the Apollo lunar landing space-

craft. A head region containing the nucleic acid is supported

on a number of spider-like legs. Upon encountering a suitable

bacterial surface, the virus acts like a syringe, to introduce the

nucleic acid into the cytoplasm of the bacterium.

Other viruses have different shapes. These include

spheres, ovals, worm-like forms, and even irregular (pleomor-

phic) arrangements. Some viruses, such as the influenzavirus,

have projections sticking out from the surface of the virus.

These are crucial to the infectious process.

As new species of eukaryotic and prokaryotic organ-

isms are discovered, no doubt the list of viral species will con-

tinue to grow.

See alsoViral genetics; Virus replication

VIRULENCE•seeMICROBIOLOGY, CLINICAL

VVirus replicationIRUS REPLICATION

Viral replication refers to the means by which virus particles

make new copies of themselves.

Virusescannot replicate by themselves. They require

the participation of the replication equipment of the host cell

that they infect in order to replicate. The molecular means by

which this replication takes place varies, depending upon the

type of virus.

Viral replication can be divided up into three phases:

initiation, replication, and release.

The initiation phase occurs when the virus particle

attaches to the surface of the host cell, penetrates into the cell

and undergoes a process known as uncoating, where the viral

genetic material is released from the virus into the host cell’s

cytoplasm. The attachment typically involves the recognition

of some host surface molecules by a corresponding molecule

on the surface of the virus. These two molecules can associate

tightly with one another, binding the virus particle to the sur-

face. A well-studied example is the haemagglutinin receptor of

the influenzae virus. The receptors of many other viruses have

also been characterized.

A virus particle may have more than one receptor mol-

ecule, to permit the recognition of different host molecules, or

of different regions of a single host molecule. The molecules

on the host surface that are recognized tend to be those that are

known as glycoproteins. For example, the human immunode-

ficiency virusrecognizes a host glycoprotein called CD4.

Cells lacking CD4 cannot, for example, bind the HIVparticle.

Penetration of the bound virus into the host interior

requires energy. Accordingly, penetration is an active step, not

a passive process. The penetration process can occur by sev-

eral means. For some viruses, the entire particle is engulfed by

a membrane-enclosed bag produced by the host (a vesicle) and

is drawn into the cell. This process is called endocytosis. Polio

virus and orthomyxovirus enters a cell via this route. A second

method of penetration involves the fusion of the viral mem-

brane with the host membrane. Then the viral contents are

directly released into the host. HIV, paramyxoviruses, and her-

pesviruses use this route. Finally, but more rarely, a virus par-

ticle can be transported across the host membrane. For

example, poliovirus can cause the formation of a pore through

the host membrane. The viral DNAis then released into the

pore and passes across to the inside of the host cell.

Once inside the host, the viruses that have entered via

endocytosis or transport across the host membrane need to

release their genetic material. With poxvirus, viral proteins

made after the entry of the virus into the host are needed for

uncoating. Other viruses, such as adenoviruses, her-

pesviruses, and papovaviruses associate with the host mem-

brane that surrounds the nucleusprior to uncoating. They are

guided to the nuclear membrane by the presence of so-called

nuclear localization signals, which are highly charged viral

proteins. The viral genetic material then enters the nucleus via

pores in the membrane. The precise molecular details of this

process remains unclear for many viruses.

For animal viruses, the uncoating phase is also referred

to as the eclipse phase. No infectious virus particles can be

detected during that 10–12 hour period of time.

In the replication, or synthetic, phase the viral genetic

material is converted to deoxyribonucleic acid(DNA), if the

material originally present in the viral particle is ribonucleic

acid(RNA). This so-called reverse transcriptionprocess needs

to occur in retroviruses, such as HIV. The DNA is imported

into the host nucleus where the production of new DNA,

RNA, and protein can occur. The replication phase varies

greatly from virus type to virus type. However, in general, pro-

teins are manufactured to ensure that the cell’s replication

machinery is harnessed to permit replication of the viral

genetic material, to ensure that this replication of the genetic

material does indeed occur, and to ensure that this newly made

material is properly packaged into new virus particles.

Replication of the viral material can be a complicated

process, with different stretches of the genetic material being

transcribed simultaneously, with some of these geneproducts

required for the transcription of other viral genes. Also repli-

cation can occur along a straight stretch of DNA, or when the

DNA is circular (the so-called “rolling circle” form). RNA-

containing viruses must also undergo a reverse transcription

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