Viruses

Medical Biology
DR. KHALID ALYODAWI
khthamer@[Link]
01/2024
The Learning outcome
1. Describe the structure of a general virus.
2. Learning about how viruses infect cells and produce their genetic materials.
Introduction
•The term microbe applies to microscopic organisms, such as
bacteria, and viruses, that are widely distributed in the
environment.
•They may be found both on non-living objects and on the
surfaces and inside plants and animals.
•While the term often is associated with diseases many of the
activities of microbes are useful to humans.
•We eat foods produced by bacteria, and bacteria contribute
to the production of yogurt, cheese, bread, and many pickled
foods.
 •Drugs available through biotechnology are produced by bacteria.
•Without the activity of decomposers*, the biosphere (including
ourselves) would cease to exist.
•When a tree falls to the forest floor, it eventually rots, because
decomposers, including bacteria and fungi, break down the
remains of dead organisms to inorganic nutrients.
•Plants need these inorganic nutrients to make the many molecules
that become food for us.
•Despite all these benefits, certain bacteria and viruses are
known as pathogens or disease-causing agents.
* decomposers are organisms that break down dead or decaying organisms
 •Our body has multiple lines of defense against bacteria and
viruses. For example:
1. Barriers to entry, such as the skin and mucous membranes of
body cavities, prevent pathogens from gaining entrance into the
body.
2. First responders, such as the phagocytic white blood cells,
prevent an infection after an invasion has occurred due to a
pathogen getting past a barrier and into the body.
3. Acquired defenses overcome infection by killing the
disease-causing agent that has entered the body.
Viruses
•Viruses bridge the gap between the living and the nonliving.
•Outside a host, viruses are essentially chemicals that can be
stored on a shelf.
•But when the opportunity arises, viruses replicate inside cells,
and during this period they appear to be alive.
•While scientists are still debating whether viruses should be
considered living, the fact is that they are acellular (not
composed of cells), and they lack the metabolic machinery
needed to acquire and use nutrients.
•Therefore, they lack the general characteristics of life.
•The largest viruses are only
about one-quarter the size
of a bacterium, about
one-hundredth the size of
a eukaryotic cell.
•However, most are much
smaller and can be viewed
only using the most
powerful microscopes.
•A virus always
has two parts: an
outer capsid
composed of Adenoviruses cause colds
protein units and
an inner core of
nucleic acid.

Influenza viruses cause the flu

•A virus carries the genetic information needed to
reproduce itself.
• In contrast to cellular organisms, the viral genetic
material need not be double-stranded DNA or even DNA.
•Some viruses, such as HIV and influenza, have RNA as
their genetic material.
•A virus may also contain various enzymes that help it
reproduce.
•Viruses are cellular parasites.
•They are microscopic pirates, commandeering the metabolic
machinery of a host cell.
•Viruses gain entry into and are specific to a particular host cell
because portions of the virus are specific for a receptor on the
host cell’s outer surface.
•Once the virus is attached, the viral genetic material (DNA or RNA)
enters the cell.
•Inside the cell, the nucleic acid codes for the protein units in the
capsid.
•In addition, the virus may have genes for special enzymes needed
for the virus to reproduce and exit from the host cell.
•In large measure, however, a virus relies on the host’s enzymes
and ribosomes for its reproduction.
•Viruses cause diseases such as colds, flu, measles, chickenpox,
polio, rabies, AIDS, genital warts, and genital herpes.
Viruses: Parasites of the Cellular Genetic
System
•Viruses are obligate, intracellular parasites.
•They cannot reproduce by themselves and must
commandeer a host cell’s machinery to synthesize viral
proteins and, in some cases, replicate the viral genome.
•RNA viruses, which usually replicate in the host-cell
cytoplasm, have an RNA genome, and DNA viruses, which
commonly replicate in the host-cell nucleus, have a DNA
genome.
•Viral genomes may be single- or double-stranded,
depending on the specific type of virus.
•The entire infectious virus particle, called a virion, consists
of nucleic acid and an outer shell of protein.
•The simplest viruses contain only enough RNA or DNA to
encode four proteins; the most complex can encode some
two hundred proteins.
Most Viral Host Ranges Are Narrow
•The surface of a virion contains many copies of one type
of protein that binds specifically to multiple copies of a
receptor protein on a host-cell surface.
•This interaction determines the host range—the group of
cell types that a virus can infect—and begins the infection
process.
•Most viruses have a relatively limited host range.
•A virus that infects only bacteria is called a bacteriophage,
or simply a phage.
•Viruses that infect animal or plant cells are referred to
generally as animal viruses or plant viruses.
•A few viruses can grow in both plants or animals and the
insects that feed on them.
•The highly mobile insects serve as vectors for transferring
such viruses between susceptible animal or plant hosts.
•Wide host ranges are also characteristic of some strictly
animal viruses, such as vesicular stomatitis virus, which
grows in insect vectors and in many different types of
mammals.
•Most animal viruses, however, do not cross phyla, and
some (e.g., poliovirus) infect only closely related species,
such as primates.
•The host-cell range of some animal viruses is further restricted to a
limited number of cell types because only those cells have surface
receptors to which the virions can attach.
•One example is poliovirus, which infects only cells in the intestine
and, unfortunately for its host, motor neurons in the spinal cord,
causing paralysis.
•Another is HIV-1, which infects cells called CD4+ T lymphocytes
that are essential for the immune response as well as certain
neurons and other cells of the central nervous system called glial
cells.
Viral Capsids
•The nucleic acid of a virion is enclosed within a protein coat, or
capsid, composed of multiple copies of one protein or a few
different proteins, each encoded by a single viral gene.
•Because of this structure, a virus can encode all the information
for making a relatively large capsid in a few genes.
•This efficient use of genetic information is important because only
a limited amount of DNA or RNA, and therefore a limited number
of genes, can fit into a virion capsid.
Lytic Viral Growth Cycles Lead to Death of Host Cells
•Although details vary among different types of viruses, those that
exhibit a lytic cycle of growth proceed through the following
general stages:
1. Adsorption (capsid protein bind to cell receptor)
2. Penetration (viral genome crosses the host plasma membrane)
3. Replication (viral mRNAs are translated by the host cell)
4. Assembly (viral proteins and replicated genomes form virions)
5. Release (lead to the death of the infected cell)
Lytic replication cycle of a nonenveloped bacterial
• The lytic cycle is somewhat more complicated for DNA viruses that infect
eukaryotic cells.
• In most such viruses, the DNA genome is transported (with some associated
proteins) into the cell nucleus.
• Once inside the nucleus, the viral DNA is transcribed into RNA by the host’s
transcription machinery.
• Processing of the viral RNA primary transcript by host-cell enzymes yields viral
mRNA, which is transported to the cytoplasm and translated into viral
proteins by host-cell ribosomes, tRNA, and translation factors.
• The viral proteins are then transported back into the nucleus, where some of
them either replicate the viral DNA directly or direct cellular proteins to
replicate the viral DNA.
• Association of the capsid proteins with the newly replicated viral DNA occurs
in the nucleus, yielding thousands to hundreds of thousands of progeny
virions.
• For example, Bacteriophage T4 replicates in and lyses E. coli cells in about 20
minutes, whereas replication of poliovirus and lysis of host cells requires
about 8 hours.
• Many animal viruses are considerably slower than poliovirus, requiring 2 days
or more for lysis of an infected cell and release of progeny virions.
• Most RNA genome viruses do not require nuclear functions for lytic
replication.
• In some of these viruses, a virus-encoded enzyme that enters the host cell
during penetration transcribes the viral genomic RNA into mRNA in the cell
cytoplasm.
• The mRNA is directly translated into viral proteins by the host-cell translation
machinery.
• One or more of these proteins then produce additional copies of the viral
RNA genome.
• Finally, progeny genomes are associated with newly synthesized capsid
proteins to form progeny virions in the cytoplasm.
•After synthesizing hundreds to hundreds of thousands of new
virions has been completed, most infected bacterial cells and
some infected plant and animal cells are lysed, releasing all the
virions at once.
•Enveloped animal viruses are surrounded by an outer
phospholipid bilayer, derived from the plasma membrane of a
host cell, that contains abundant viral glycoproteins.
•To illustrate the lytic replication of enveloped viruses, we consider
the rabies virus, whose nucleocapsid consists of a single-stranded
RNA genome bound by multiple copies of a nucleocapsid protein.
•Like other lytic RNA viruses, the rabies virus is replicated in the
cytoplasm and does not require host-cell nuclear enzymes.
Lytic replication cycle of an enveloped
Viral DNA Is Integrated into the Host-Cell
Genome in Some Nonlytic Viral Growth
Cycles
• Some bacterial viruses, called temperate phages, can establish a nonlytic association
with their host cell that does not kill the cell.
• For example, when bacteriophage λ (Lambda) infects E. coli, most of the time it
causes a lytic infection.
• Occasionally, however, the viral DNA is integrated into the host-cell chromosome
rather than being replicated.
• The integrated viral DNA, called a prophage, is replicated as part of the host cell’s
DNA from one host-cell generation to the next.
• This phenomenon is referred to as lysogeny.
• If the host cell suffers extensive damage to its DNA from UV light, the prophage DNA
is activated, leading to its excision from the host-cell chromosome, entrance into the
lytic cycle, and subsequent production and release of progeny virions before the host
cell dies.
• The genomes of a number of animal viruses can also integrate into the
host-cell genome.
• Among the most important of these are the retroviruses, which are
enveloped viruses with a genome consisting of two identical strands of RNA.
• These viruses are so named because their RNA genome acts as a template for
the formation of a DNA molecule—a flow of genetic information that is
opposite to the more common transcription of DNA into RNA.
•In the retroviral life cycle, a viral enzyme called reverse
transcriptase initially copies the viral RNA genome into
single-stranded DNA that is complementary to the viral RNA; the
same enzyme then catalyzes the synthesis of a complementary
DNA strand.
• The resulting double-stranded DNA is integrated into the chromosomal DNA
of the infected cell by an integrase enzyme in the virion.
• Finally, the integrated DNA, called a provirus, is transcribed by the host cell’s
own RNA polymerase into RNA, which is either translated into viral proteins
or packaged within virion capsid proteins to form progeny virions that are
released by budding from the host-cell membrane.
• Because most retroviruses do not kill their host cells, infected cells can
replicate, producing daughter cells with integrated proviral DNA.
• These daughter cells continue to transcribe the proviral DNA and bud progeny
virions.
Retroviral life
•Some retroviruses contain cancer-causing genes (oncogenes), and
cells infected by such retroviruses are oncogenically transformed
into tumor cells.
•Studies of oncogenic retroviruses (mostly viruses of birds and
mice) have revealed a great deal about the processes that lead to
transformation of a normal cell into a cancer cell
References
•Mader, S. S., Windelspecht, M. (2017). Human Biology. United Kingdom: McGraw-Hill Education.
•Lodish, H. F. (2016). Molecular cell biology. Macmillan.