2Overview of Topic What is a virus? Human virus infections Treatment DefinitionStructure and replicationHuman virus infectionsTreatmentAntiviralsVaccinesVaccination against virusesInactivated vaccinesLive vaccinesInterferon
3What is a Virus?A virus is a non-cellular particle made up of genetic material and protein that can invade living cellsStructureCore of nucleic acid surrounded by a protein coat called a capsidCapsid can be DNA or RNA, but not bothCore can be several to several hundred genes
41 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 nm1 nanometer (nm) = one billionth of a metereukaryotic cells 10, ,000 nmviroids nmviruses nmprion 2-10 nm
5VIRUS SHAPES Round Herpes virus There are two types: Genital oral Rod-shapedTobacco mosaic virusMany sided (icosohedral)
6SHAPES MAY DIFFER BUT… All viruses have 1. Chromosome-like part that carries hereditary information – The Core2. Protein coat: Protects hereditary information and provides the shape! The CapsidInfluenza VirusTobacco MosaicVirusT4 BacteriophageDNAcapsidtail sheathtail fiber
9VIRUSES ARE SPECIFIC IN THE CELLS THEY INFECT Specificity – usually infect specific organismsCannot infect animals if it infects plantsSome can infect wider varietyRabies – all mammals, some birdsCommon cold: infects cells on airway passage to lungsTobacco mosaic virus: only tobacco plants…not wheat or cornRabies: only nervous system cells of mammals
10Viroid A viroid is made only of single-stranded RNA. causes disease in plantscan stunt plant growthpassed through seeds or pollen
11Bacteriophage E coli bacteria Bacteriophages are viruses that infect bacteriaBacteriophageHead – capsid and DNATail – with fibers to attach to bacteriaT groupMost 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
12Viruses need living organisms in order to reproduce and form more viruses! Injecting DNAvirus
13Retroviruses RNA viruses When they infect a cell, they produce DNA copies of their RNA genes.Retroviruses have their genetic information copied backwards. RNA DNAOne retrovirus is HIV. Others cause cancer in animals and humans.
14Viruses enter host cell in different ways: Bacteriophages pierce host cellsViruses of eukaryotes enter by endocytosisViruses of eukaryotes also fuse with membrane
16Virus Replication 1 2 3 4 5 6 7 8 Virus attachment and entry Uncoating of virion3Migration ofgenome nucleicacid to nucleus4Transcription5Genome replication7Virion assembly6Translation of virusmRNAs8Release of newvirus particles
17SO HOW DO VIRUSES CAUSE DISEASE? Section 19-3Bacteriophage protein coatBacteriophage DNABacterialchromosomeBacteriophage attaches to bacterium’s cell wallBacteriophage enzyme lyses theBacterium’s cell wall, releasingnew bacteriophage particles that can attack other cells.Lytic CycleBacteriophage injects DNA into bacteriumBacteriophage proteins and nucleic acids assemble into complete bacteriophage particlesBacteriophageBacteriophage DNABacteriophage proteinBacteriophage takes over bacterium’s metabolism, causing synthesis of new bacteriophage proteins and nucleic acids
18Lytic 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.GrowthBacterium 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.ReplicationVirus 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.
19Lysogenic 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.
20Types 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 infectionThe outcome of some virus infections is not cell death but the development of a persistent (or chronic) virus infection.Latent InfectionThe 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 cellTransformationA 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.
21Transmission of Viruses Respiratory transmissionInfluenza A virusFecal-oral transmissionEnterovirusBlood-borne transmissionHepatitis B virusSexual TransmissionHIVAnimal or insect vectorsRabies virus·
22Targeting of the virus to specific tissue and cell types Receptor RecognitionCD4+ cells infected by HIVCD155 acts as the receptor for poliovirusAcute Virus InfectionsLocalised to specific site of bodyDevelopment of viraemia with widespread infection of tissues
23Viruses and Disease Examples are: Small Pox Polio Measles AIDS Mumps InfluenzaYellow FeverRabiesCommon ColdHerpesEbola etc…
24Human immunodeficiency virus HIVHuman immunodeficiency virusIs a retrovirus (virus that contains RNA and uses an enzyme to make a DNA copy).DNA is usually made from RNACan remain dormant for many yearsDestroys white blood cells of the host’s immune systemHIV-infected whiteblood cell
25Chicken Pox - ShinglesChicken 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.
26Hepatitis AA 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.
27Hepatitis BInflammation 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).
28Hepatitis CLiver 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.
29Influenza A virus Properties of the virus Myxovirus Enveloped virus with a segmented RNA genomeInfects a wide range of animals other than humansUndergoes extensive antigenic variationMajor cause of respiratory infections
30Influenza A virus Infection Spread by respiratory routeVirus infects cells of the respiratory tractDestruction of respiratory epitheliumSecondary bacterial infectionsDuring 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.
31Common Cold There are more than 200 viruses that can cause a cold They can mutateSARSSevere Acute Respiratory Syndrome is a viral respiratory disease.Causes fever, coughing, difficulty breathing
33Poliovirus Poliovirus vaccines Properties of the virus Enterovirus. BEnterovirus.Possesses a RNA genome.Transmitted by the fecal oral route.Cause of gastrointestinal illness and poliomyelitis.403020101950196019701980Number of cases (in thousands)Poliovirus vaccinesA: Salk – killed inactivatedvaccine.B: Sabin – live attenuatedvaccine
34Poliovirus Infection Gut Viraemia Paralysis Non-neuronal tissues Virus excretionin the faecesNon-neuronaltissuesViraemiaNeuronaltissuesParalysis·
35Generation of Novel Influenza A Viruses Avian H3N8Human H2N2ANTIGENIC SHIFTGenetic ReassortmentHuman H3N2Point mutation of HA and NAgenesANTIGENIC DRIFT
36Viruses and Human Tumours Epstein Barr VirusBurkitt’s LymphomaHuman papillomavirusBenign wartsCervical CarcinomaHuman T-cell Leukaemia Virus (HTLV-1)LeukaemiaHepatitis C virusLiver carcinoma
37Virus-induced tumours InfectionUninfectedCellUncontrolled cellgrowth and tumourformation?
38Virus-induced transformation Normal cellsTransformed cellsVirus 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.
39Treatment and Prevention of Virus Infections AntiviralsTarget:Attachment/EntryPicornavirusesNucleic acid replicationHuman immunodeficiency virus (AZT)Herpes simplex virus (Acyclovir)Virus protein processingHIV (Protease inhibitors)Virus maturationInfluenza A virus (Neuraminidase blockers)Vaccines and immunizationsThe body’s own defenses must be usedVaccine – dead or weakened viruses that stimulate the bodies defense systemSymptoms can be treated sometimes, but once someone is infected by a virus, there is not much science can do
40Problems with Antivirals Identification of virus-specific target.Difficulty in finding a virus specific site against which to direct the antiviralGeneration 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.
41InterferonInterferons 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.