1. Viruses

2. Overview of Topic What is a virus? Human virus infections Treatment
Definition
Structure and replication
Human virus infections
Treatment
Antivirals
Vaccines
Vaccination against viruses
Inactivated vaccines
Live vaccines
Interferon

3. What is a Virus?
A virus is a non-cellular particle made up of genetic material and protein that can invade living cells
Structure
Core of nucleic acid surrounded by a protein coat called a capsid
Capsid can be DNA or RNA, but not both
Core can be several to several hundred genes

4. 1 nanometer (nm) = one billionth of a meter
SO HOW BIG ARE VIRUSES?
Viruses are REALLY small.
Size – 20 to 400 nanometers (one nanometer is one billionth of a meter)
They are much smaller than bacteria.
They can only be seen with an electron microscope.
prokaryotic cells ,000 nm
1 nanometer (nm) = one billionth of a meter
eukaryotic cells 10, ,000 nm
viroids nm
viruses nm
prion 2-10 nm

5. VIRUS SHAPES Round Herpes virus There are two types: Genital oral
Rod-shaped
Tobacco mosaic virus
Many sided (icosohedral)

6. SHAPES MAY DIFFER BUT… All viruses have
1. Chromosome-like part that carries hereditary information – The Core
2. Protein coat: Protects hereditary information and provides the shape! The Capsid
Influenza Virus
Tobacco Mosaic
Virus
T4 Bacteriophage
DNA
capsid
tail sheath
tail fiber

7. Virion Structure Lipid Envelope Nucleic Acid Protein Capsid Virion
Spike
Projections
Protein
Capsid
Lipid Envelope
Virion
Associated
Polymerase
·        

9. VIRUSES ARE SPECIFIC IN THE CELLS THEY INFECT
Specificity – usually infect specific organisms
Cannot infect animals if it infects plants
Some can infect wider variety
Rabies – all mammals, some birds
Common cold: infects cells on airway passage to lungs
Tobacco mosaic virus: only tobacco plants…not wheat or corn
Rabies: only nervous system cells of mammals

10. Viroid A viroid is made only of single-stranded RNA.
causes disease in plants
can stunt plant growth
passed through seeds or pollen

11. Bacteriophage E coli bacteria
Bacteriophages are viruses that infect bacteria
Bacteriophage
Head – capsid and DNA
Tail – with fibers to attach to bacteria
T group
Most commonly studied are T group – T1, T2, T3, T4 etc...
T4 has a DNA core within a protein coat, and tail with tail fibers to attach to bacteria.
E coli bacteria

12. Viruses need living organisms in order to reproduce and form more viruses!
Injecting DNA
virus

13. Retroviruses RNA viruses
When they infect a cell, they produce DNA copies of their RNA genes.
Retroviruses have their genetic information copied backwards. RNA  DNA
One retrovirus is HIV. Others cause cancer in animals and humans.

14. Viruses enter host cell in different ways:
Bacteriophages pierce host cells
Viruses of eukaryotes enter by endocytosis
Viruses of eukaryotes also fuse with membrane

16. Virus Replication 1 2 3 4 5 6 7 8 Virus attachment and entry
Uncoating of virion 3
Migration of
genome nucleic
acid to nucleus 4
Transcription 5
Genome replication 7
Virion assembly 6
Translation of virus
mRNAs 8
Release of new
virus particles

17. SO HOW DO VIRUSES CAUSE DISEASE?
Section 19-3
Bacteriophage protein coat
Bacteriophage DNA
Bacterial
chromosome
Bacteriophage attaches to bacterium’s cell wall
Bacteriophage enzyme lyses the
Bacterium’s cell wall, releasing
new bacteriophage particles that can attack other cells.
Lytic Cycle
Bacteriophage injects DNA into bacterium
Bacteriophage proteins and nucleic acids assemble into complete bacteriophage particles
Bacteriophage
Bacteriophage DNA
Bacteriophage protein
Bacteriophage takes over bacterium’s metabolism, causing synthesis of new bacteriophage proteins and nucleic acids

18. Lytic Infection Cause cells to lyse or burst Infection
chance contact virus with right kind of bacterium.
Virus attaches to bacterium and injects its DNA.
Most times, complete virus particle does not enter.
Growth
Bacterium cannot tell difference between bacterial and viral DNA.
RNA polymerase causes mRNA to be made from cell for virus.
Viral DNA takes over and produces more DNA and viral proteins.
Replication
Virus uses bacterial material to make thousands of copies of the protein coat and DNA.
Cell becomes filled with virus particles. (All three stages can happen with E. coli within 25 minutes!)
DNA serves as central point for virus particles to be assembled. Cells fill with virus and lyse (burst). New viruses can now infect new cells.

19. Lysogenic cycle- a virus imbeds its DNA into the DNA or the host cell and is replicated along with the host cell’s DNA. Bacterial DNA called prophage.

20. Types of Infections Cell death – Cytopathic effect
This is the end result of many lytic virus infections in which the cell is killed following virus infection.
Persistent infection
The outcome of some virus infections is not cell death but the development of a persistent (or chronic) virus infection.
Latent Infection
The capacity of herpes virus to establish a latent infection is essentially another form of persistent infection. In this case the virus is not actually replicating but lying dormant in the host cell
Transformation
A transformed cell in vitro or a tumour developing in vivo is essentially a cell-type, which shows no control over its cell division with unregulated growth.

21. Transmission of Viruses
Respiratory transmission
Influenza A virus
Fecal-oral transmission
Enterovirus
Blood-borne transmission
Hepatitis B virus
Sexual Transmission
HIV
Animal or insect vectors
Rabies virus
·        

22. Targeting of the virus to specific tissue and cell types
Receptor Recognition
CD4+ cells infected by HIV
CD155 acts as the receptor for poliovirus
Acute Virus Infections
Localised to specific site of body
Development of viraemia with widespread infection of tissues

23. Viruses and Disease Examples are: Small Pox Polio Measles AIDS Mumps
Influenza
Yellow Fever
Rabies
Common Cold
Herpes
Ebola etc…

24. Human immunodeficiency virus
HIV
Human immunodeficiency virus
Is a retrovirus (virus that contains RNA and uses an enzyme to make a DNA copy).
DNA is usually made from RNA
Can remain dormant for many years
Destroys white blood cells of the host’s immune system
HIV-infected white
blood cell

25. Chicken Pox - Shingles
Chicken Pox and shingles are both caused by varicella-zoster, a member of the herpes virus family. Chicken Pox is an uncomfortable, highly contagious and sometimes serious disease.
Chicken Pox preventable by vaccine and it’s very unusual to acquire more than once in immunocompetent persons.
The virus remains in your body and can later reactivate and become shingles.  

26. Hepatitis A
A liver disease that results from infection with the Hepatitis A virus.
It can range in severity from a mild illness lasting a few weeks to a severe illness lasting several months.
Hepatitis A is usually spread when a person ingests fecal matter — even in microscopic amounts — from contact with objects, food, or drinks contaminated by the feces or stool of an infected person.
Almost all people who get Hepatitis A recover completely and do not have any lasting liver damage, although they may feel sick for months.

27. Hepatitis B
Inflammation of the liver due to the hepatitis B virus (HBV).
It can also be transmitted via needle sticks, body piercing and tattooing using unsterilized instruments, the dialysis process, sexual and even less intimate close contact, and childbirth.
Symptoms include fatigue, jaundice, nausea, vomiting, dark urine, light stools.
Diagnosis is by blood test.
Treatment is via anti-viral drugs and/or hepatitis B immunoglobulin (HBIG).

28. Hepatitis C
Liver disease that results from infection with the Hepatitis C virus.
It can range in severity from a mild illness lasting a few weeks to a serious, lifelong illness.
Hepatitis C is usually spread when blood from a person infected with the Hepatitis C virus enters the body of someone who is not infected. (Most commonly by sharing needles or other equipment to inject drugs).
Before 1992, when widespread screening of the blood supply began in the United States, Hepatitis C was also commonly spread through blood transfusions and organ transplants.
Hepatitis C can be either “acute” or “chronic.” Acute Hepatitis C virus infection is a short-term illness that occurs within the first 6 months after someone is exposed to the Hepatitis C virus. For most people, acute infection leads to chronic infection. Chronic Hepatitis C is a serious disease than can result in long-term health problems, or even death.

29. Influenza A virus Properties of the virus Myxovirus
Enveloped virus with a segmented RNA genome
Infects a wide range of animals other than humans
Undergoes extensive antigenic variation
Major cause of respiratory infections

30. Influenza A virus Infection
Spread by respiratory route
Virus infects cells of the respiratory tract
Destruction of respiratory epithelium
Secondary bacterial infections
During a sneeze, millions of tiny droplets of water and mucus are expelled at about 100 miles per hour with 100,000 germs into the air.

31. Common Cold There are more than 200 viruses that can cause a cold
They can mutate
SARS
Severe Acute Respiratory Syndrome is a viral respiratory disease.
Causes fever, coughing, difficulty breathing

32. Poliovirus
·       

33. Poliovirus Poliovirus vaccines Properties of the virus Enterovirus.B
Enterovirus.
Possesses a RNA genome.
Transmitted by the fecal oral route.
Cause of gastrointestinal illness and poliomyelitis. 40 30 20 10
1950
1960
1970
1980
Number of cases (in thousands)
Poliovirus vaccines
A: Salk – killed inactivated
vaccine.
B: Sabin – live attenuated
vaccine

34. Poliovirus Infection Gut Viraemia Paralysis Non-neuronal tissues
Virus excretion
in the faeces
Non-neuronal
tissues
Viraemia
Neuronal
tissues
Paralysis
·        

35. Generation of Novel Influenza A Viruses
Avian H3N8
Human H2N2
ANTIGENIC SHIFT
Genetic Reassortment
Human H3N2
Point mutation of HA and NA
genes
ANTIGENIC DRIFT

36. Viruses and Human Tumours
Epstein Barr Virus
Burkitt’s Lymphoma
Human papillomavirus
Benign warts
Cervical Carcinoma
Human T-cell Leukaemia Virus (HTLV-1)
Leukaemia
Hepatitis C virus
Liver carcinoma

37. Virus-induced tumours
Infection
Uninfected
Cell
Uncontrolled cell
growth and tumour
formation [ ] ?

38. Virus-induced transformation
Normal cells
Transformed cells
Virus transformed cells show a complete deregulation of their normal growth. They tend to pile up over each other and do not stop growing as is typical of normal uninfected/non-transformed cells.
This change in the phenotype is due to the virus influencing the gene regulation of the cell. Many of the cellular genes affected that lead to the transformed phenotype are associated with growth regulation and signal recognition.

39. Treatment and Prevention of Virus Infections
Antivirals
Target:
Attachment/Entry
Picornaviruses
Nucleic acid replication
Human immunodeficiency virus (AZT)
Herpes simplex virus (Acyclovir)
Virus protein processing
HIV (Protease inhibitors)
Virus maturation
Influenza A virus (Neuraminidase blockers)
Vaccines and immunizations
The body’s own defenses must be used
Vaccine – dead or weakened viruses that stimulate the bodies defense system
Symptoms can be treated sometimes, but once someone is infected by a virus, there is not much science can do

40. Problems with Antivirals
Identification of virus-specific target.
Difficulty in finding a virus specific site against which to direct the antiviral
Generation of resistant variants.
As with the use of antibiotics – resistant mutant scan be readily generated that are resistant to antivirals – this is particularly a problem with those against HIV where the drug has to be used for prolonged periods of time.

41. Interferon
Interferons are a family of naturally-occurring proteins that are made and secreted by cells of the immune system (for example, white blood cells, natural killer cells, fibroblasts, and epithelial cells).
Since interferons enhance the immune system in many ways, they are used for many diseases that involve the immune system.
Examples:
Interferon alfa-2a (Roferon-A)
Interferon alfa-2b - malignant melanoma, chronic hepatitis C, and chronic hepatitis B.
Ribavirin combined with interferon alfa-2b, interferon alfacon-1 (Infergen), pegylated interferon alfa-2b, or pegylated interferon alpha-2a, all are approved for the treatment of chronic hepatitis C.
Interferon beta-1b (Betaseron) and interferon beta-1a (Avonex) are approved for the treatment of multiple sclerosis.
Interferon alfa-n3 (Alferon-N) is approved for the treatment of genital and perianal warts caused by human papillomavirus (HPV).
Interferon gamma-1B (Actimmune) is approved for the treatment of chronic granulomatous disease, and severe, malignant osteopetrosis.