1. Viruses cause the most common acute infectious disease in the USA today - that being the common cold.

2. It has been estimated that the average person experiences between 3 to 6 diseases due to viral infections per year or more than 200-400 instances of viral diseases over one’s life time.

3. Viruses account for 50% of absenteeism from work and school

4. Children experience any more viral infection per year. On the average, children see their physician at least 7 times a year.

5. These diseases caused by viruses vary widely in their severity. Some viruses cause diseases, such as diarrhea and the common cold, whose symptoms are mildly discomforting. Other viruses, such as rabies virus, cause a fatal disease, encephalitis.

6. In addition, we will see that viral infections can occur, not only in adults, children and infants, but also can take place “ in utero”. These intrauterine infections can lead to significant morbidity and mortality

Small ("filterable")

Obligatory intracellular parasites (= require living host cells to multiply)

Some bacteria are similar in this respect: rickettsiae and chlamydiae

Contain a single type of NA.

Contain a protein coat, sometimes itself enclosed by an envelope of lipids, proteins, and carbohydrates, that surrounds the NA.

Multiply inside living cells by using the synthesizing machinery of the cell.

Cause the synthesis of specialized structures that transfer the viral NA to other cells.

Small intracellular parasites that cannot reproduce on their own.

Host range is used to classify viruses:  bacteriophage, animal viruses, plant viruses.

Genome consists of either RNA or DNA (3-100 genes).

Nucleic acid is either ss or ds.

Cells (prokaryotic and eukaryotic):

• DNA is always the primary genetic material
• RNA plays an auxilliary role

Viruses

• Either DNA or RNA, never both, is the primary genetic material
• NA is either single stranded or double stranded
• NA is either linear or circular

Typical Bacteria vs. Viruses

Growth of Animal Viruses

• in cell culture
• in embryonated eggs (caution for egg allergies when vacines are cultured this way)
• in living animals (BUT, some human viruses cannot be grown in animals or they can be grown by do not cause disease)

A complete viral particle is composed of NA surrounded by a coat that:

• protects it from the environment
• serves as a vehicle of transmission

Structure:

• NA is surrounded by a protein coat (=capsid)
• Capsid is composed of capsomeres
• Capsomeres:  of a single type or many types of proteins
• The arrangement of capsomeres is characteristic of a particular type of virus

A virus whose capsid is not covered by an envelope

[image]

1.  Icosahedral

[image]

2.  Helical

[image]

Envelope:  covers capsid in some viruses

Usually:  a combination of lipids, proteins, and carbohydrates

In some viruses, envelope contains proteins of host cell's plasma membrane (stolen from the host cell).

In some viruses, the envelope contains proteins determined by viral NA and material derived from the normal cell components.

Envelope may be covered by spikes (serve as attachment proteins).

[image]

Viruses containing lipid envelopes are sensitive to desiccation in the environment and are often transmitted by the respiratory, parenteral and sexual routes.

Non-enveloped viruses are stable in harsh environmental conditions and often are transmitted by the fecal-oral route.

Current classification has 3 criteria:

• The type and structure of the viral NA and the strategy used in its replication
• The type of symmetry of the virus capsid
• The presence or absence of a lipid envelope

[image]

Viruses are fundamentally different from other microorganisms:

• Require an intact cell in order to replicate
• Can direct the synthesis of thousands of progeny virus during a single cycle
• No replication by fission

A virus must invade a host cell and take over the host's metabolic machinery.

Enzymes needed for protein synthesis, ribosomes, tRNA, and energy production are supplied by the host cell and used for synthesis of viral proteins, including viral enzymes.

Result:  a single virus gives rise to thousands of viruses in a single host cell.  This process frequently results in cell's death.

1.  Attachment

2.  Penetration

3.  Disassembly (uncoating)

4.  Replication (of viral genome and proteins)

5.  Assembly

6.  Maturation and release

[image]

Receptor sites for viruses:  proteins and glycoproteins of the plasma membrane.  Either highly specialized proteins with limited tissue distribution (complement receptors, growth factor receptors, neurotransmitter receptors) or ubiquitous components (integrins, phospholipids, sialic acid).

Viral attachment proteins:  spikes or capsid proteins

Typically viruses utilize multiple mechanisms of attachment.

Potential for drugs.

Typically by endocytosis:  an active cellular process

After endocytosis:  destruction of viral envelope

Separation of the viral nucleic acid from its protein coat

DNA viruses = in or near the nucleus

RNA viruses = cytoplasm

The viral genome has a dual function:

• To make mRNA and viral proteins
• Lots of replica of its genome 

DNA viruses = in nucleus

RNA viruses = cytoplasm

Viral protein synthesis takes place in the cytoplasm.

[image]

[image]

[image]

[image]

[image]

[image]

Red = RNA viruses (cytoplasm)

Blue = DNA viruses (nucleus)

Assembly of the protein capsid is usually spontaneous.

Assembled capsid-containing NA pushes through the plasma membrane.

Viral pathogenesis is the process by which virus interacts with its host in a discrete series of stages to produce disease.

Viral pathogenesis:  the capacity of the virus to produce disease in a susceptible host.

1.  Entry into the host

2.  Primary replication

3.  Spread

4.  Cell and tissue tropism

5.  Secondary replication

6.  Cell injury or persistence

7.  Host immune response

Exposure of a susceptible host to viable virus under conditions that promote infection.

Virus may be present in:

• Repiratory droplets or aerosols
• Recally contaminated food or water
• Body fluid (blood, saliva, urine, semen) or tissue (transplanted organs)
• Direct inoculation (insect bite or contaminated needle)

Mother to infant transmission:

• virus carried in a germ line
• virus infecting the placenta or birth canal
• virus in breast milk

Reactivation of endogenous latent virus rather than de novo exposure.

Acute Viral Infection

Many febrile diseases

Short incubation period

Recovery or death (~2 weeks)

Sometimes asymptomatic or subclinical

Persistent:  virus remains in equilibrium within the host and does or does not produce a disease

Persistent:  months or years

4 Types:

• Latent
• Chronic
• Slow
• Oncogenic

Persistent (Latent) Viral Infection

Acute infection with apparent recovery - herpetic gingivostomatitis

 Small amounts of virus sequestered

Later recurrence of acute symptoms - herpes labialis

Virus persists in large quantity over a long period

Virus continuously detectable - hepatitis B

Long incubation period

Gradual, inexorable progression

Death

Subacute sclerosing panencephalitis, progressive encephalitis, progressive focal leukoencephalopathy (mental deterioration, brain degeneration)

Subacute sclerosing panencephalitis, secondary to measles

Integration of viral genetic information into host cell chromosome, leads to tumor production

Burkitt's lymphoma (caused by EBV)

~ 40 approved in the US

Three categories:

• Agents that directly inactivate intact viruses (=virucides)
• Agents that modify the host response (=immunomodulators)
• Agents that inhibit viral life cycle at the cellular leve (=antivirals)

Agents that cause direct inactivation - detergents, organic solvents (ether or chloroform), ultraviolet light

Problems:  not useful in treatment

Treatments that destroy both host tissues and virus simultaneously:  cryotherapy, laser, podophyllin

Use:  prevention of transmission in discrete mucocutaneous infections

Intact host immunologic responses remain essential for recovery from virus infections.

Problem:  many antiviral agents may blunt host immune responses by direct immunisuppressive effects or by altering humoral and cellular immune responses indirectly through reductions in viral antigen exposure.

Agents used to treat infections

Agents used to replace deficient host immune responses such as exogenous antibody (chronic echovirus infections) cytotoxic T lymphocytes (CMV infection in bone marrow recipients).

Agents that enhance endogenous defenses, many under investigation, one used currently (Imiquimod, in genital HPV).

• attachment to the cell
• uncoating the viral genome
• assembly of progeny virions
• inhibit virus-directed (as opposed to host cell-directed) macromolecular synthesis

1.  Attachment

2.  Penetration

3.  Disassembly (uncoating)

4.  Replication of viral genome and proteins

5.  Assembly

6.  Maturation and release

Problems with this:

1.  Viral replication depends primarily on host cell metabolic functions, therefore many agents that in vitro inhibit viral replication also affect host's function.

2.  Current antiviral agents are not effective in the elimination of non-replicating or latent viruses.

3.  Viruses develop resistance.