Pharmaceutical Microbiology

Virology

What are Viruses?

It is a small infectious agent that replicates only inside the living cells of other organisms. It can infect all types of life forms, from animals and plants to bacteria and archaea.

The main purpose of a virus is to deliver its genome into the host cell to allow its expression (transcription and translation) by the host cell.

Virus Properties
Virus is defined as a nucleoprotein complex which infects cells and uses their metabolic processes to replicate Smallest known infective agents Metabolically inert - no metabolic activity outside host cell; must enter host cell to replicate Most are highly species specific

Virus versus Virion

Virus is a broad general term for any aspect of the infectious agent and includes: the infectious or inactivated virus particle viral nucleic acid and protein in the infected cell Virion is the physical particle in the extra-cellular phase which is able to spread to new host cells; complete intact virus particle

Characteristics of Infectious Microorganisms

Property
Size (nm) Nuclear structure Obligate intracellular Nucleic acids Culture on Artificial media

Bacteria
100 -10,000 Prokaryotes No

Viruses
30 - 300 ---Yes

Fungi
4,000 - 40,000 Eukaryotes No

Protozoa
4,000 - 40,000 Eukaryotes No

DNA/RNA Haploid Yes

DNA or RNA

DNA/RNA

DNA/RNA

No

Yes

Yes

Relative Sizes of Microorganisms

Limits of resolution

50,000-V electron microscope 0.003 m

Light microscope 0.2 m

Unaided human eye 40 m Microscopic protozoa & fungi 4 - 40 m

Classes of organisms

Viruses 0.03 - 0.3 m

Bacteria 0.1 - 10 m

0.001

0.01

0.1 Size (m)

10

100

History of Virology
Virus discovery came about when the cause of an infectious disease could not be explained by the presence of bacteria Observation of a virus under electron microscopy and the development of cell tissue culture started the golden era of virology Eradication of smallpox following a worldwide vaccination program

CLASSIFICATION OF VIRUSES
(1) Nucleic acid type: RNA or DNA; single-stranded or doublestranded; strategy of replication. (2) Size and morphology, including type of symmetry, number of capsomeres, and presence of membranes. (3) Presence of specific enzymes, particularly RNA and DNA polymerases, and neuraminidase (4) Susceptibility to physical and chemical agents, especially ether. (5) Immunologic properties. (6) Natural methods of transmission. (7) Host, tissue, and cell tropisms. (8) Pathology; inclusion body formation. (9) Symptomatology.

Classification Parameters
Several Parameters Are Used for Classification
Viral classification study is referred to as Taxonomy 73 families exist so far!! Type of genomic nucleic acid Size of virion and genome Capsid structure Host Replication mechanism

Viruses: Structures

Viral Nucleic Acid

Polymeric macromolecules essential for all known forms of life DNA: deoxyribonucleic acid RNA: ribonucleic acid

Viral Capsid
Protein shell of a virus Protect the viral nucleic acid from detrimental chemical and physical conditions Characterized by the shape of the capsid Capsomere basic unit of a capsid

Viral Capsid
Icosahedral Helical

Icosahedral capsid
Constructed from 12 pentamers

Prolate Capsid

Helical Capsid

Viral Envelope
Lipidic envelope that surrounds the viral capsid Originates from the host cells Added during the replication process or following excision of the viral progeny from the host cells It fuses with the host membrane allowing the capsid and viral genome to enter and infect the host

Viral Receptors
Structures protruding from the viral envelope Glycoproteins and proteins

Baltimore Classification System

Class 1: ds DNA Virus Class 2: ss DNA Virus Class 3: ds RNA Virus Class4 and 5: ss RNA
Class 4: ss RNA Virus Positive Sense Class 5: ss RNA Negative Sense

Class 6:Positive sense ss RNA Class 7: ds DNA that replicate through a ss RNA intermediate

Class 1: ds DNA Virus

Usually must enter the host nucleus before it is able to replicate Replication of the viral genome is highly dependent on a cellular state permissive to DNA replication and thus on the cell cycle

Class 2: ss DNA Virus

They replicate within the nucleus and form a ds DNA intermediate during replication

Class 3: ds RNA Virus

Do not rely on host polymerases for replication to the extent that viruses with DNA genomes do

Class4 and 5: ss RNA

Class 4: ss RNA Virus Positive Sense can be directly accessed by host ribosomes to immediately form proteins Class 5: ss RNA Negative Sense viruses containing non-segmented genomes for which the genes cannot be directly accessed by host ribosomes They must be transcribed by viral polymerases into readable complementary positive sense

Class 6:Positive sense ss RNA

Reverse transcriptase and integrase

Class 7: ds DNA that replicate through a ss RNA intermediate

Hepatitis B form a ccc DNA (covalently closed circle DNA)

Virus Host Cell interaction

All viruses have to solve three different problems to persist in nature:

Replication inside the cell Movement from one cell (and host) to another Evasion of host antiviral defenses

What is viral pathogenesis?

Viruses must infect cells to replicate. Virally infected cells often, but not always, die as a result of the infection a phenomenon usually described in tissue culture as cytopathic effect (CPE). The intention of the host response is to destroy virally infected cells and rid the host of the virus. The good news is that many virally infected cells are destroyed as a result of the immune response. The bad news is that the intense antiviral response often does collateral damage to noninfected cells within the organ bearing a viral infection and causes immunopathology. The combinations of virus-induced cell dysfunction and CPE and host response-induced cell destruction are the basic processes involved in viral pathogenesis.

Examples of organ-specific effects of viral pathogenesis:

Viral infection of the central nervous system usually results in meningitis, encephalitis or meningoencephalitis. Viral infections of the respiratory tract are among the most common infections of man.

No matter what the organ system, the basis of viral pathogenesis is the same -viruses targeting a certain population of human cells in a given organ system and causing a combination of direct cell destruction and an elicited host response that contributes to cell and organ dysfunction (immunopathogenesis).