Medical Microbiology II Lecture 7

MEDICAL MICROBIOLOGY II

Lesson 6

Basic Virology Part I

Viruses

Virology

Virology is the study of viruses

Viruses are the smallest infectious agents (20 to 300 nm in diameter)

They are entirely dependent on the host cell for biosynthesis of macromolecules

They behave like living chemicals

Viruses infect unicellular organisms such as bacteria and algae, and all higher plants and animals

Morphology of Viruses

1. Size

Most viruses are too small to be seen with the light microscope

The size ranges from 20 nm to 300 nm

The poxviruses are the largest (300 nm) and are about the same size as the smallest bacteria

Poxviruses can be seen with the light microscope

All other viruses are visible only under the electron microscope


The size of a virus can be measured by:

1. Filtration through collodion membranes of graded porosity

2. Direct observation and measurement in the electron microscope

3. Determination of the sedimentation rate in the ultracentrifuge

4. Comparative measurements with other microorganisms of known sizes


2. Structure

Complete virus particle = VIRION

Virion consists of a nucleic

acid core surrounded by an

impenetrable protein coat,

the capsid

The capsid is composed of a large number of morphological units called capsomers


Capsid + nucleic acid core = NUCLEOCAPSID

The capsomers are symmetrically arranged around the core


The capsid has 5 functions:

1. Protects the core

2. Helps it to enter into the host cell site of receptors to mediate attachment to hosts cell

3. Provide structural symmetry of the virus

4. Serve as antigenic determinants

5. Induce antibody production


There are 2 types of symmetrical arrangement of the capsid around the core: icosahedral and helical

However, a few viruses have a complex structure (e.g. poxviruses)

Icosahedral and Helical Viruses


1. Icosahedral symmetry

A polygon with 12 vertices (corners) and 20 facets (sides)

Each facet is a equilateral triangle

Usually formed independent of nucleic acid

e.g. adenovirus

Icosahedral Viruses

Icosahedral Naked Viruses


2. Helical symmetry

Capsomers are bound to the nucleic acid in such a way that the nucleic acid winds spirally to form a helix

Involves interaction between the nucleic acid core and the capsid

e.g. tobacco-mosaic virus, orthomyxoviruses

Helical Viruses

Helical Naked Virus


3. Complex structure

Some viruses do not exhibit symmetry, but are complex in structure

e.g. poxviruses are brick shaped with ridges on the external surface

Complex Viruses


4. Envelope

Some viruses have a covering outside the capsid = envelope (virus is said to be enveloped)

The envelope is derived from the host cell membrane when the virus is released from the cell

Envelope is made up of lipids and proteins

The protein subunits may project from the envelope as spikes

Enveloped viruses

Chemical Constituents of Viruses

Viruses are made up of:

1. Proteins

2. Nucleic acid

3. Lipids

4. Carbohydrates


1. Proteins

Capsid (protective covering) consists of proteins

Antigenic characteristics of the virus

Some are in the form of enzymes

These enzymes are essential for the initiation of the replication cycle of the virus within the host cell


e.g. orthomyxoviruses contain RNA polymerase, while retroviruses contain reverse transcriptase (enzyme that makes complementary copy of RNA)


2. Nucleic Acid

Either DNA or RNA:

single or double stranded

circular or linear in shape

may or may not be segmented

Nucleic acid: contain genetic information necessary for the replication of the virus

Sequences and composition of nucleotides are specific for each virus

Useful in classifying viruses into families


3. Lipids

In the envelopes of viruses

As envelopes is formed by budding from the cell membrane of the host cell lipid composition

e.g. herpesviruses bud through the nuclear membrane of the host cell lipid composition of the nuclear membrane instead of the cell membrane


4. Carbohydrates

Viral envelopes also contain glycoprotein coded by the virus itself

Helps in attachment to the host cells

Glycoproteins are also involved in the interactions with antibodies due to their antigenic nature

Classification of Medically Important Viruses

Classification of viruses depends on their structure, antigenic composition and other properties

Viruses are classified into 2 major divisions depending on the type of nucleic acid

I. Deoxyriboviruses, which contain DNA

II. Riboviruses, which contain RNA

Both of these are further subdivided mainly on size and shape of the virion, symmetry of the nucleocapsid and strandedness of the nucleic acid


I. DNA viruses

1. Family Parvoviridae

Size : 18 - 26 nm

Symmetry: Icosahedral

Envelope: Absent

DNA: Single stranded

Example: Parvovirus - cause gastroenteritis


2. Family Papovaviridae

Size : 40 - 55 nm


Envelope: Absent

DNA: Double stranded

Example: Papilloma virus - causes cutaneous, genital and laryngeal warts

Polyomavirus - causes neurological diseases


3. Family Adenoviridae

Size : 70 - 90 nm


Envelope: Absent


Example: Adenovirus. There are at least 41 types of adenoviruses that can infect humans. They attack the lymphoid tissue and the mucous membranes. Some adenoviruses can cause acute respiratory disease, and conjunctivitis.


4. Family Herpesviridae

Size : 100 - 200 nm


Envelope: Present


Example: Herpes simplex virus - HSV type 1 may cause oral infection or keratitis; HSV type 2 causes genital lesions, Varicella / Zoster - causes chicken pox as primary infection


These viruses may remain latent in the nerve ganglia and may be reactivated when the immunity is lowered, resulting in shingles

Cytomegalovirus (CMV) - causes severe generalised neonatal infection or an infection similar to glandular fever in adults; generalised infection may occur in immunosuppressed patients, especially in AIDS

Epstein-Barr virus - causes infectious mononucleosis, also associated with Burkitts lymphoma


5. Family Poxviridae

Size : 300 - 450 nm x 170 - 260 nm (brick-shaped)

Symmetry: Unknown

Envelope: Present


Example: Poxviruses produce skin lesions (e.g.smallpox)


6. Family Hepadnaviridae

Size : 42 nm

Symmetry: Unknown

Envelope: Present

DNA: Partially double stranded

Example: Hepatitis B virus may be transmitted from person to person by inoculation with infected blood e.g. from a contaminated hypodermic syringe and needle.


The virus can cause hepatitis, liver cirrhosis and hepatocellular carcinoma


II. RNA viruses

1. Family Picornaviridae

Size : 22 - 30 nm


Envelope: Absent

RNA: Single stranded

Example: Rhinoviruses (more than 100 serotypes which cause the common cold),


Enteroviruses (e.g. Poliovirus, Echovirus and Coxsackie virus), these viruses are ingested and multiply in the GI tract.

They spread to the tissues and organs to which they have affinity, via the blood stream. The viruses are excreted in the faeces


Poliovirus causes poliomyelitis, an acute infectious disease and affects the central nervous system. It destroys the motor neurons in the spinal cord resulting in paralysis. There are 3 serotypes (1, 2 and 3). An oral vaccine prepared from attenuated strains of the 3 serotypes provides effective immunization.


Coxsackie virus is divided into 2 groups (A and B). They produce a variety of illness in humans. Herpangina, hand, foot and mouth disease, and acute haemorrhagic conjunctivitis are caused by some group A coxsackie virus

Group B serotypes are associated with myocarditis, pericarditis and meningoencephalitis


Both groups are responsible for aseptic meningitis, respiratory and undifferentiated febrile illness, hepatitis and paralysis. The paralysis is incomplete and reversible.

Echoviruses (about 30 serotypes). Some cause aseptic meningitis, febrile illnesses with or without rash, and common cold


New enteroviruses. Newly recognised enteroviruses are given numbers instead of names. Hepatitis A virus is now renamed as Enterovirus type 72.


2. Family Reoviridae

Size : 60 - 80 nm


Envelope: Absent

RNA: Double stranded

Example: Reoviruses and Rotaviruses. Reoviruses cause minor febrile illnesses, diarrhoea or enteritis and are not known to cause any severe illness. Rotaviruses are a major cause of diarrhoea in infants and children.


3. Family Orthomyxoviridae

Size : 100 nm, spherical or pleomorphic

Symmetry: Helical

Envelope: Present

RNA: Single stranded, segmented in 8 pieces

Example: All Orthomyxoviruses are Influenza viruses (types A, B and C). Influenza is an acute respiratory tract infection which usually occurs in epidemics.


They have on their surface, projections that exhibit haemagglutinin and neuraminidase activity. Antigenic variation is observed very frequently in group A serotypes and less frequently in group B serotypes. Type C is antigenically stable.


4. Family Paramyxoviridae

Size : 150 - 300 nm, spherical or pleomorphic

Symmetry: Helical

Envelope: Present

RNA: Single stranded, non-segmented

Example: Mumps virus - causes an acute contagious disease characterised by a non-suppurative enlargement of one or both of the parotid glands.


Measles (Rubeola) virus - causes an acute, highly infectious disease characterised by a maculopapular rash and fever and is associated with respiratory involvement. Parainfluenza viruses - cause serious illnesses such as laryngotracheitis and croup, bronchitis, and pneumonitis, especially in the first year of life. Respiratory Syncytial virus (RSV) - causes the most serious bronchiolitis.


5. Family Rhabdoviridae

Size : 50 - 95 x 130 - 390 nm, bullet-shaped

Symmetry: Helical

Envelope: Present


Example: Rabies virus - causes an acute infection of the central nervous system that is almost always fatal. The transmission of the virus is usually through the bite of a rabid animal such as dog.


6. Family Bunyaviridae

Size : 90 - 120 nm

Symmetry: Helical

Envelope: Present

RNA: Single stranded, triple segmented

Example: the name of this virus is derived from Bunyawera (Uganda), where this virus was first isolated. The majority are transmitted to vertebrates by arthropods.


Other members include arboviruses that cause Rift Valley fever and of the Crimean-Congo haemorrhagic group.


7. Family Coronaviridae

Size : 80 - 130 nm, pleomorphic with large, clubbed projections

Symmetry: Helical

Envelope: Present


Example: Human coronaviruses which cause common colds and gastroenteritis in infants


8. Family Togaviridae

Size : 40 - 70 nm


Envelope: Present


Example: Rubella virus - causes an acute febrile illness with rash and lymphadenopathy. It affects children and young adults. Infection in the early pregnancy may result in abnormalities of the foetus.


Arboviruses (arthropode-borne viruses) - many arboviruses are from the family Togaviridae, e.g. Yellow fever virus, which causes an acute, febrile mosquito borne illness. Severe cases may show jaundice, proteinuria and haemorrhage

Other example of arboviruses are Chikugunya, Semliki Forest and Sindbis viruses


9. Family Arenaviridae

Size : 50 - 300 nm

Symmetry: Complex, pleomorphic

Envelope: Present


Example: Members of this family are rodent parasites which occasionally infect man, causing haemorrhagic illness, e.g. Lassa virus.


10.Family Retroviridae

Size : 80 - 100 nm

Symmetry: Unknown

Envelope: Present


Example: Members of this family contain a unique enzyme, reverse transcriptase, which is an RNA directed DNA polymerase.


The family has many tumour producing viruses such as the Sarcoma viruses of birds and mice, and the leukaemia viruses of mice, cats, birds and humans.

The Human Immunodeficiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS) is also included in this family.


III. Arboviruses

Viruses of vertebrates biologically transmitted by insect vectors

Multiply in blood sucking insect vectors e.g.mosquitoes and ticks

Transmitted to vertebrates through insect bites

Grouping is based on ecological and epidemiological considerations


The name arboviruses is a biological rather than taxonomical concept

Human pathogens include Dengue virus, Yellow fever virus, Encephalitis viruses, Chikungunya virus, Sandfly fever virus and Rift Valley fever virus

Taxonomically, arboviruses belong to families Togaviridae, Bunyaviridae, Reoviridae and Rhabdoviridae


IV. Unclassified Viruses

Some viruses have not been classified due to insufficient information to permit classification

Includes those viruses causing immune complex diseases, those causing slow virus disease and some gastroenteritis viruses

Replication of Viruses

Viruses need living cells to multiply

The host cells provides:

The synthetic machinery, the precursors, and the energy for the synthesis of viral proteins and nucleic acids

The viral nucleic acid codes for the genetic information

General outline of replication cycle is similar


Can be divided into 4 sequential phases:

1. Phase I: Adsorption

2. Phase II: Penetration and Uncoating

3. Phase III: Biosynthesis of Virus Components

4. Phase IV: Maturation and Release


1. Phase I: Adsorption

Viruses come into contact with host cells maybe through random collision

Adsorption can only happen if the host cell has specific receptors to which the virus can attach itself

Receptor molecules differ for different viruses, e.g. the picornaviruses need protein receptors while orthomyxo- and paramyxoviruses need oligosaccharide receptors


Specificity of interaction between viruses and host cell receptors may vary, e.g. lipoprotein receptors for polioviruses are present on the cells of the central nervous system of primates only, and so they can infect only primates

However, togaviruses can absorb to a wide range of hosts such as birds, mosquitoes, horses and humans


2. Phase II: Penetration and Uncoating

Penetration begins almost immediately after absorption

During penetration, the virus particle is taken up in the host cell viropexis

Penetration is associated with the removal of the capsid or viral envelope from the nucleic acid or nucleoprotein core uncoating


Penetration and uncoating can occur in at least two different ways:

Virus particles appear fuse with or become engulfed by the cytoplasmic membrane and are transported directly into the cytoplasm as naked particles

Some viruses may be phagocytosed and appear internally in the cell in vacuoles, which eventually break down, releasing the virus into the cytoplasm

After uncoating, infectivity of the virus particle is lost till it completes its replicative cycle eclipse period

Duration of this period varies depending on individuals viruses and the host

Ends with the formation of the first progeny of the virus particles

Viruses are the only infectious agents which require the dissolution of the infecting agent in the process of replication


3. Phase III: Biosynthesis of Virus Components

Includes the synthesis of viral nucleic acid, capsid proteins, and the enzymes necessary in the various stages of virus synthesis

The proteins and regulatory enzymes which are required to shut down normal cellular metabolism of the host cell and direct sequential production of viral products are also synthesised during this phase


The biosynthesis may be summarised as:

i. Transcription of messenger RNA (mRNA) from the viral nucleic acid

ii. Translation of mRNA into early proteins which are enzymes needed to initiate and maintain the synthesis of viral components and suppression of cell metabolism

iii. Replication of viral nucleic acid

iv. Synthesis of late structural proteins which are components of the viral capsid


As a general rule, DNA viruses synthesise their nucleic acid in the nucleus, while RNA viruses produce their nucleic acid in the cytoplasm


4. Phase IV: Maturation and Release

Newly synthesised viral genomes and capsid proteins assemble together to form progeny viruses

Icosahedral capsids can condense in the absence of nucleic acid, while viruses with helical symmetry need viral RNA for the formation of the capsid

Progeny of non-enveloped viruses are complete


The infected host cell eventually lyses and releases the newly formed virus particles

Enveloped viruses are released by the process of budding through the cell membrane

Virus specific envelope glycoproteins are inserted into the cellular membrane

Viral nucleocapsids then bud through these modified sites, acquiring an envelope in the process


Enveloped viruses are not infectious until they have acquired their envelopes infectious progeny virions do NOT accumulate within the infected cell

Release by Budding

Lytic and Lysogenic Replication Cycle

THE END

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Medical Microbiology II Lecture 7

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