5. introduction to viruses

Program PGMIPABIFakultas Keguruan dan Ilmu PendidikanUniversitas Syiah Kuala

An Introduction to the Viruses

History (1)

• For many years, the cause of viral infections such as smallpox and polio was unknown, even though it was clear that the diseases were transmitted from person to person. • The French bacteriologist Louis Pasteur was certainly on the right

track when he postulated that rabies was caused by a “living thing” smaller than bacteria,

• in 1884 he was able to develop the first vaccine for rabies. • Pasteur also proposed the term virus to denote this special

group of infectious agents.

Program PGMIPABI-FKIP Unsyiah

History (2)

• The first substantial revelations about the unique characteristics of viruses occurred in the 1890s. • First, D. Ivanovski and M. Beijerinck showed that a disease in

tobacco was caused by a virus (tobacco mosaic virus). • Friedrich Loeffler and Paul Frosch discovered a virus that causes

foot-and-mouth disease in cattle. • These early researchers found that when

infectious fluids from host organisms were passed through porcelain filters designed to trap bacteria, the filtrate remained infectious.


History (3)

• Over the succeeding decades, a remarkable picture of the physical, chemical, and biological nature of viruses began to take form.

• Years of experimentation were required to show that viruses were noncellular particles with a definite size, shape, and chemical composition.

• Using special techniques, they could be cultured in the laboratory. • By the 1950s, virology had grown into a multifaceted discipline

that promised to provide much information on disease, genetics, and even life itself


The Position of Viruses in the Biological Spectrum

• Viruses are a unique group of biological entities known to infect every type of cell, including bacteria, algae, fungi, protozoa, plants, and animals.

• it is best to describe viruses as infectious particles (rather than organisms) and as either active or inactive (rather than alive or dead).

• Viruses are different from their host cells in size, structure, behavior, and physiology. • They are a type of obligate intracellular parasite that cannot

multiply unless it invades a specific host cell and instructs its genetic and metabolic machinery to make and release quantities of new viruses.


Properties of Viruses



General Structure of Viruses

• As a group, viruses represent the smallest infectious agents.

• Their size places them in the realm of the ultramicroscopic . • This term means that most of them are so minute (<0.2 μm)

that an electron microscope is necessary to detect them or to examine their fine structures.


Size comparison of viruses with a eukaryotic cell (yeast) and bacteria. Viruses range from largest (1) to smallest (9). A molecule of a large protein (10) is included to indicate proportion of macromolecules.

The Size of Viruses


Viral Components: Capsids, Nucleic Acids,and Envelopes (1)

• The general plan of virus organization is the utmost in simplicity and compactness.

• Viruses contain only those parts needed to invade and control a host cell: • an external coating and a core containing one or more

nucleic acid strands of either DNA or RNA.


Viral Components: Capsids, Nucleic Acids,and Envelopes (2)


Capsids (1)

• All viruses have capsids - protein coats that enclose and protect their nucleic acid.

• Each capsid is constructed from identical subunits called capsomers made of protein.

• The capsid together with the nucleic acid are nucleoscapsid.

• Some viruses have an external covering called envelope; those lacking an envelope are naked.


Capsids (2)

Generalized structure of viruses. (a) The simplest virus is a naked virus (nucleocapsid) consisting of a geometric capsid assembled around a nucleic acid strand or strands. (b) An enveloped virus is composed of a nucleocapsid surrounded by a flexible membrane called an envelope. The envelope usually has special receptor spikes inserted into it.


Capsids (3)

• Two structural types: • helical - continuous helix of capsomers forming

a cylindrical nucleocapsid• The nucleocapsids of naked helical viruses are very rigid and

tightly wound into a cylinder-shaped package. Ex: TMV• Enveloped helical nucleocapsids are more flexible and tend

to be arranged as a looser helix within the envelope. Ex: influenza, measles, and rabies viruses

• icosahedral - 20-sided with 12 corners• vary in the number of capsomers

• a poliovirus has 32, and an adenovirus has 242 capsomers• Each capsomer may be made of 1 or several proteins.


Helical capsids

Typical variations of viruses with helical nucleocapsids. Naked helical virus (tobacco mosaic virus): (a) a schematic view and (b) a greatly magnified micrograph. Note the overall cylindrical morphology. Enveloped helical virus (influenza virus): (c) a schematic view and (d) a colorized micrograph featuring a positive stain of the avian influenza virus. This virus has a well-developed envelope with prominent spikes termed H5N1 type.


Icosahedral viruses (1)


Icosahedral viruses (2)

Two types of icosahedral viruses, highly magnified. (a) Upper view: A negative stain of rotaviruses with unusual capsomers that look like spokes on a wheel; lower view is a threedimensional model of this virus. (b) Herpes simplex virus, a type of enveloped icosahedral virus.


Viral envelope

• When enveloped viruses (mostly animal) are released from the host cell, they take with them a bit of its membrane system in the form of an envelope. • Some viruses bud off the cell membrane; others leave via

the nuclear envelope or the endoplasmic reticulum.• Some proteins form a binding layer between the envelope

and capsid of the virus, and glycoproteins (proteins bound to a carbohydrate) remain exposed on the outside of the envelope. • These protruding molecules, called spikes or peplomers,

are essential for the attachment of viruses to the next host cell.


Functions of Capsid/Envelope

• The outermost covering of a virus is indispensable to viral function • it protects the nucleic acid from the effects of

various enzymes and chemicals when the virus is outside the host cell.

• Capsids and envelopes are also responsible for helping to introduce the viral DNA or RNA into a suitable host cell, • by binding to the cell surface • by assisting in penetration of the viral nucleic acid


Complex viruses: atypical viruses (1)

• Two special groups of viruses, termed complex viruses are more intricate in structure than the helical, icosahedral, naked, or enveloped viruses just described.

• Poxviruses lack a typical capsid and are covered by a dense layer of lipoproteins.

• Some bacteriophages have a polyhedral nucleocapsid along with a helical tail and attachment fibers.


Complex viruses: atypical viruses (2)

Detailed structure of complex viruses. (a) Section through the vaccinia virus, a poxvirus, shows its internal components. (b) Photomicrograph and (c) diagram of a T4 bacteriophage.


Basic types of viral morphology

A. Complex viruses: (1) poxvirus, a large DNA virus (2) flexible-tailed bacteriophageB. Enveloped viruses:• With a helical nucleocapsid: (3) mumps virus(4) rhabdovirus• With an icosahedral nucleocapsid: (5) Herpesvirus (6) HIV (AIDS)

C. Naked viruses:• Helical capsid: (7) plum poxvirus• Icosahedral capsid: (8) Poliovirus ; (9) papillomavirus


Nucleic acids (1)

• Viral genome – either DNA or RNA but never both

• Carries genes necessary to invade host cell and redirect cell’s activity to make new viruses

• Number of genes varies for each type of virus – few to hundreds


Nucleic acids (2)

• DNA viruses • usually double stranded (ds) but may be single

stranded (ss)• circular or linear

• RNA viruses • usually single stranded, may be double stranded,

may be segmented into separate RNA pieces• ssRNA genomes ready for immediate translation are

positive-sense RNA.• ssRNA genomes that must be converted into proper

form are negative-sense RNA.


Other Substances in the Virus Particle

• In addition to the protein of the capsid, the proteins and lipids of envelopes, and the nucleic acid of the core, viruses can contain enzymes for specific operations within their host cell.

• They may come with preformed enzymes that are required for viral replication. • polymerases that synthesize DNA and RNA and replicases that

copy RNA.

• The AIDS virus comes equipped with reverse transcriptase for synthesizing DNA from RNA.

• However, viruses completely lack the genes for synthesis of metabolic enzymes. • this deficiency has little consequence, because viruses have

adapted to assume total control over the cell’s metabolic resources.


How Viruses Are Classified and Named (1)

• Classified based on structures, size, nucleic acids, host species, target cells.

• 3 orders, 63 families, and 263 genera of viruses• Family name ends in -viridae • Genus name ends in -virus, Simplexvirus,

Hantavirus, Enterovirus• Name of genus or family begins with

description of virus • appearance: togavirus, coronavirus• place collected: adenovirus, hantavirus• effect on host: lentivirus• acronymns: picornavirus; hepadnavirus


How Viruses Are Classified and Named (2)


DNA VIRUS


RNA VIRUS


Modes of Viral Multiplication (1)

• General phases in animal virus multiplication cycle:1. Adsorption - binding of virus to specific

molecule on host cell2. Penetration - genome enters host cell3. Uncoating – the viral nucleic acid is released

from the capsid4. Synthesis – viral components are produced5. Assembly – new viral particles are

constructed6. Release – assembled viruses are released by

budding (exocytosis) or cell lysis


Modes of Viral Multiplication (2)

General features in the multiplication cycle of an enveloped animal virus. Using an RNA virus (rubella virus), the major events are outlined, although other viruses will vary in exact details of the cycle.


Adsorption and Host Range (1)

• Virus coincidentally collides with a susceptible host cell and adsorbs specifically to receptor sites on the cell membrane

• Spectrum of cells a virus can infect – host range• hepatitis B – human liver cells• poliovirus – primate intestinal and nerve cells• rabies – various cells of many mammals


Adsorption and Host Range (2)

The mode by which animal viruses adsorb to the host cell membrane. (a) An enveloped coronavirus with prominent spikes. The configuration of the spike has a complementary fit for cell receptors. The process in which the virus lands on the cell and plugs into receptors is termed docking. (b) An adenovirus has a naked capsid that adheres to its host cell by nestling surface molecules on its capsid into the receptors on the host cell’s membrane.


Penetration/Uncoating (1)

• Flexible cell membrane is penetrated by the whole virus or its nucleic acid by:• endocytosis – entire virus is engulfed and

enclosed in a vacuole or vesicle• fusion – envelope merges directly with

membrane resulting in nucleocapsid’s entry into cytoplasm


Penetration/Uncoating (2)

Two principal means by which animal viruses penetrate. (a) Endocytosis (engulfment) and uncoating of a herpesvirus. (b) Fusion of the cell membrane with the viral envelope (mumps virus).



Replication and Protein Production

• Varies depending on whether the virus is a DNA or RNA virus

• DNA viruses generally are replicated and assembled in the nucleus.

• RNA viruses generally are replicated and assembled in the cytoplasm.• Positive-sense RNA contain the message for

translation.• Negative-sense RNA must be converted into

positive-sense message.


Assembly: Filling the capsid

• Capsid proteins made in cytoplasm • DNA or RNA gets fills empty capsids • final modifications to capsid • to plug any holes from DNA/RNA entry • to mature the outer proteins


Release (1)

• Assembled viruses leave host cell in one of two ways:• budding – exocytosis; nucleocapsid binds to

membrane which pinches off and sheds the viruses gradually; cell is not immediately destroyed

• lysis – nonenveloped and complex viruses released when cell dies and ruptures

• A fully formed, extracellular virus particle that is virulent (able to establish infection in a host) is called a virion

• Number of viruses released is variable• 3,000-4,000 released by poxvirus• >100,000 released by poliovirus


Release (2)

Maturation and release of enveloped viruses. As parainfluenza virus is budded off the membrane, it simultaneously picks up an envelope and spikes.



Damage to Host Cell

• Cytopathic effects - virus-induced damage to cells

1. Changes in size & shape2. Cytoplasmic inclusion bodies3. Nuclear inclusion bodies4. Cells fuse to form multinucleated cells.5. Cell lysis6. Alter DNA7. Transform cells into cancerous cells


Persistent Infections (1)

• Persistent infections - cell harbors the virus and is not immediately lysed

• Can last weeks or host’s lifetime; several can periodically reactivate – chronic latent state• measles virus – may remain hidden in brain

cells for many years• herpes simplex virus – cold sores and genital

herpes• herpes zoster virus – chickenpox and shingles


Persistent Infections (2)

• Some animal viruses enter host cell and permanently alter its genetic material resulting in cancer – transformation of the cell.

• Transformed cells have increased rate of growth, alterations in chromosomes, and capacity to divide for indefinite time periods resulting in tumors.

• Mammalian viruses capable of initiating tumors are called oncoviruses. • Papillomavirus – cervical cancer• Epstein-Barr virus – Burkitt’s lymphoma


Multiplication Cycle in Bacteriophages

• Bacteriophages – bacterial viruses (phages)• Most widely studied are those that infect

Escherichia coli – complex structure, DNA• Multiplication goes through similar stages as

animal viruses. • Only the nucleic acid enters the cytoplasm -

uncoating is not necessary.• Release is a result of cell lysis induced by viral

enzymes and accumulation of viruses - lytic cycle.


6 Steps in Phage Replication

1. Adsorption – binding of virus to specific molecule on host cell

2. Penetration –genome enters host cell3. Replication – viral components produced4. Assembly - viral components assembled5. Maturation – completion of viral formation6. Release – viruses leave cell to infect other cells




Penetration & Release of Phage

Penetration of a bacterial cell by a T-even bacteriophage and A weakened bacterial cell, crowded with viruses.


Lysogeny: The Silent Virus Infection

• Not all phages complete the lytic cycle.• Some DNA phages, called temperate phages,

undergo adsorption and penetration but don’t replicate.

• The viral genome inserts into bacterial genome and becomes an inactive prophage - the cell is not lysed.

• Prophage is retained and copied during normal cell division resulting in the transfer of temperate phage genome to all host cell progeny – lysogeny.

• Induction can occur resulting in activation of lysogenic prophage followed by viral replication and cell lysis.


Techniques in Cultivating and Identifying Animal Viruses (1)

• Obligate intracellular parasites that require appropriate cells to replicate

• Methods used:• cell (tissue) cultures – cultured cells grow in

sheets that support viral replication and permit observation for cytopathic effect

• bird embryos – incubating egg is an ideal system; virus is injected through the shell

• live animal inoculation – occasionally used when necessary



Cell Culture



Cultivating animal viruses in a developing bird embryo


Detection of Animal Viral Infections

• More difficult than other agents• Consider overall clinical picture• Take appropriate sample • Infect cell culture – look for characteristic

cytopathic effects• Screen for parts of the virus• Screen for immune response to virus

(antibodies)


Diagnosis


Treatment of viral infections

• The nature of viruses has at times been a major impediment to effective therapy. • Because viruses are not bacteria, antibiotics aimed at bacterial

infections do not work.

• While there are increasing numbers of antiviral drugs, most of them block virus replication by targeting the function of host cells. This can cause severe side effects.

• Antiviral drugs are designed to target one of the steps in the viral life cycle you learned about earlier in this chapter. • Azidothymide (AZT), a drug used to treat AIDS, targets the nucleic acid

synthesis stage. • A newer class of HIV drugs, the protease inhibitors, disrupts the final

assembly phase of the viral life cycle.• Another compound that shows some potential for treating and preventing

viral infections is a naturally occurring human cell product called interferon

• Vaccines that stimulate immunity are an extremely valuable tool but are available for only a limited number of viral diseases


Important viruses you should know…

• Smallpox (variola major, minor) – complex virus; inclusions

• Herpesviridae – (herpes; chicken pox – varicella zoster); chronic latent state reactivated; nuclear inclusions

• HPV – can transform cells; warts cervical cancer• Hepatovirus (A, B, C)• SARS – coronavirus (like the virus that causes

bronchitis); prominent spikes on envelope• influenza – Flu; Type A is the one you’ve had;• Rotavirus – viral food poisoning; vomiting and

diarrhea – sometimes concurrently!!• HIV – retrovirus; latency;


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5. introduction to viruses