Importance of Viruses 1. Cause many diseases in plants, animals & humans • Some viruses are easily controlled with a vaccine − Mumps, Measles, Smallpox, Polio • Some viruses are difficult to control with a vaccine − Retroviruses (HIV: ssRNA dsDNA)− Common cold, Influenza (Flu), HIV 1. Used as vectors in biotechnology • Used to insert therapeutic genes into a host cell chromosome • Use viruses with provirus in life cycle
Herpes (dsDNA dsDNA) Cold sores Herpes virus may rest inactive inside host cells for long periods
Adenovirus (dsDNA) Adenoviruses cause various respiratory diseases
Polio Virus (ssRNA serves as mRNA) Polio is easily prevented with a vaccine
Measles (ssRNA template for mRNA synthesis) Measles: a childhood disease that can be prevented with a vaccine
Couple at AIDS quilt (HIV: ssRNA dsDNA) HIV is very difficult to control with a vaccine
1918 Influenza epidemic (ssRNA template for mRNA synthesis) >20 million died of the flu during WW I A new influenza vaccine must be developed yearly
Enter H5N1, the avian flu virus
Why do new strains of influenza and bird flu arise in Asia?
Background: Influenza Virus Structure (1 of 3) 1. Flu viruses are named by the type of surface proteinsa. Hemagglutinin • Helps virus enter cell • Type A infects humans, birds and pigs • Type A has ~ 20 different sub Flu Viruses Currently infecting… types • Humans: H1N1, H1N2, and H3N2• Avian Flu Virus: H5N1
Background: Influenza Virus Structure (2 of 3) 2. Named for the type of surface proteinsa. Neuraminidase• Helps virus exit cell • 9 subtypes • Currently infecting Humans: H1N1, H1N2, and H3N2
Background: Influenza Virus Structure (3 of 3) 3. Influenza viral genome• ssRNA • 8 segments (pieces) • One gene per segment Avian Flu Virus: H5N1 • Transmitted from birds to humans • No evidence of human to human transmission • Antiviral drugs: Tamiflu − a neuraminidase inhibitor − Consequences of its action?
Genetic Changes in Influenza Viruses 1. Antigenic drift – due to errors in replication and lack of repair mechanism to correct errors • Results in ___ changes 2. Antigenic shift – reassortment of genetic materials when concurrent infection of different viral strains occurs • Results in ___ changes
Emergence of New Influenza Subtypes: H5N1Antigenic shift due to genome reassortment within intermediate hosts drives flu epidemics and pandemics Solid lines: transmission demonstrated; Dotted lines: transmission postulated but not demonstrated. Source: http://www.cdc.gov/ncidod/EID/vol12no01/05-1024-G1.htm 1. Nonpathogenic H5 influenza virus: Wild fowl domestic ducks and geese, domestic chickens. 2. H5 virus became highly pathogenic in chickens domestic ducks and geese. 3. Highly Pathogenic H5 virus reassorted its genome with those of other influenza viruses in aquatic birds, spread to poultry farms, humans, and occasionally to pigs.
Where do the “new flu” viruses come from? Antigenic Drift: mutations result in changes to the Hemagglutinin (HA) molecules – RNA replication is error prone- New HA types are created frequently- Requires new vaccine every “season”- What is a vaccine?
Vaccines: Protection against viruses 1. What is a vaccine? 2. Vaccines stimulate the production of memory cel s • Give longterm protection against a specific antigen 3. Why are vaccines ineffective against the flu virus? • Why wil this year’s flu vaccine be ineffective next year? 4. Why are vaccines effective against DNA viruses? – e.g. small pox and polio virus
Smallpox (dsDNA dsDNA) Smallpox has been irradicated worldwide due to a very successful vaccine Why are vaccines for DNA viruses so successful?
Hepatitis B—an RNA virus Hepatitis B Infections may lead to liver cancer. Why? Carry viral oncogene
Viruses and Cancer Tumor Viruses: may transform normal cells into cancer cells Hepatitis B Liver cancer HTLV 1 leukemia (Human T-Cell Leukemia Virus) • Tumor viruses form a permanent provirus • Viral oncogenes code for growth factors Growth factors Stimulate cell to enter S phase » G or G S phase 1 0 • Each of the following must happen for cancer to occur Active host oncogenes + Active viral oncogenes cancer Activators of host oncogenes • Carcinogens, radiation, some viruses
Emerging viruses Ebola Hanta Virus Virus Both viruses: ssRNA template for mRNA synthesis Either virus usually results in death within days!
Deer Mouse: Carries Hanta virus in Feces
Mottling of Squash and Tobacco by the Mosaic Virus Viruses can spread easily from cell to cell via the plasmodesmata junctions between cells
Tobacco mosaic virus (RNA virus)
Comparing the size of a virus, a bacterium, and a eukaryotic cell Viral Size Millions can fit on pinhead Smaller than a ribosome!
TMV Adenovirus Influenza virus Bacteriophage T4 Viral structure
Viral Structure 1. Nucleic Acid + Protein Coat (Capsid) • Some viruses with Membrane (envelope) surrounding capsid − Envelope derived from plasma membrane of host cell− Helps virus infect host cell • No organelles • Obligate intracellular parasite • Lacks metabolic enzymes, ribosomes, mitochondria • Alone, can only infect host cell 2. Nucleic Acid: DNA or RNA • Single or Double Stranded • 4 genes to a few hundred
Class Type of Nucleic Acid Classes of Animal I. dsDNA Viruses Papavavirus Papilloma (Human warts, Cervical Cancer Grouped by Type of Adenovirus Respiratory diseases Nucleic Acid Herpesvirus Herpes Simplex I (Cold sores)Herpes Simplex II (genital sores) Varicella zoster (chicken pox) Poxvirus Smallpox; cowpox II. ssDNA Parvovirus Usually depends on co-infections w/adenovirus III. dsRNA Reovirus Diarrhea IV. ssRNA that serves as mRNA Picornavirus Poliovirus Rhinovirus: Common cold V. ssRNA that is a template for mRNA synthesis Rhabdovirus Rabies Paramyxovirus Measles, mumps Orthomyxovirus Influenza (flu) VI. ssRNA that serves as a template for DNA synthesis Retrovirus HIV (AIDS virus)RNA tumor viruses (e.g. leukemia viruses)
Host Range Host cell Recognition • Complementary fit between external viral proteins and host cell surface proteins • Some have a Broad host range Swine flu and rabies viruses • Some have a narrow host range Single tissue in a single species • e.g. Adenovirus, HIV • Phages of E. coli
Viral Reproduction Simplified DNA Virus Life Cycle • E.g. smallpox, herpes, chickenpox • “Lock and Key” fit between viral surface proteins and host cell receptors initiates endocytosis
Electron micrograph of Bacteriophage T4 Bacteriophages are viruses that infects bacteria
Bacteriophage Reproduction Bacteriophages (Bacterial Viruses) • Best understood of all viruses • Responsible for many advances in molecular biology Hershey-Chase expmts that showed that DNA is the genetic material Restriction Enzymes used in Genetic Engineering come from bacteria Lytic Cycle of Bacteriophage T4 • T4 is a Virulent Phage • Lyses host death of host cell
The lytic cycle of phage T4
Lytic and Lysogenic reproductive cycles of phage λ , a temperate phage What is the adaptive value of forming a prophage? Lytic Lysogenic Cycle Cycle Prophage
The reproductive cycle of an enveloped Virus RNA viruses • RNA serves as template to produce mRNA e.g. viruses that cause rabies, measles, mumps, flu DNA viruses • DNA serves as template to produce mRNA Herpes (Cold sores, genital herpes) Smallpox Adenovirus
AIDS: Acquired Immunodeficiency Syndrome • AIDS—caused by HIV infection • HIV = Human Immunodeficiency Virus HIV infecting a Helper T-Cell
AIDS around the world (Source: UNAIDS) New HIV Deaths from Children (under 15) cases in 2002 Aids in 2002 with Aids by end of Part of the World People with HIV 2002 North America 980,000 45,000 15,000 10,000 Sub-Saharan 29.4m 3.5m 2.4m 2.8m Africa South & 6m 700,000 440,000 240,000 Southeast Asia India: 3.9 m Latin America 1.5m 150,000 60,000 45,000 East Asia & 1.2m 270,000 45,000 4,000 Pacific Caribbean 440,000 60,000 42,000 20,000
The Structure of HIV: A Retrovirus (RNA virus) Envelope protein Carbohydrate Lipid envelope Reverse Transcriptase Protein Capsid made of protein RNA (2 copies of its genome)
Animation of HIV Life Cycle Questions to Address: 1. Why does HIV infect a specific cel type, Thelper cells (CD4 cells)? 1. What is HIV’s Genetic material? 2. What are the roles of Reverse Transcriptase, integrase, and protease? 3. How can knowledge of HIV’s life cycle be used to develop antiHIV treatments? 4. Reverse Transcriptase does not “proof read” like DNA polymerase does. a. What are the consequences? b. Of what adaptive value is this?
HIV primarily infects T-Helper Cells! • Why does HIV have a narrow host range? • Why does the virus that causes rabies have a broad host range? HIV 1.) Binding 2.) Fusion 3.) Infection Envelopeprotein Capsid CD4 RNA Receptor Cytoplasm of white blood cell protein Helper protein (T-Helper Cell) Plasma membrane of T-helper cell
O verview of H IV’s R eproductive C ycle Reverse Viral RNA What’s happening? transcriptase DNA of host cell 1. 1 Provirus DNA Nucleus DNA strand 2. 2 Double- 3 stranded DNA 4 3. 5 Viral 4. Cytoplasm RNA and proteins 6 5. 6.
R eproductive C ycle of H IV— the details! HIV Entry Reverse transcriptase Viral RNA Viral RNAcopied Integrase to viral DNA Viral DNA Viral RNA integrates intocell chromosomesand makes more Synthesis viral RNA Protease cleaves large of HIV proteins proteins into smaller ones HIV envelope proteinscome to cell surface HIV assemblesand buds from cell
Treatm ents for H IV 1. Vaccines have been unsuccessful—why? 1. Reverse Transcriptase Inhibitors Block viral DNA formation from viral RNA 2. DNA base analogs Block DNA elongation • e.g. AZT, 3TC (3-thiocytosine) 1. Protease Inhibitors Block enzymes that process envelope proteins 2. Why use a “Shotgun” approach? 3. Possible future treatments: • Plug drugs—drugs that plug receptors for HIV on surface of host cell • Vaccines
Evolutionary Origin of Viruses Evolved from fragments of Cellular Nucleic Acids Evidence 1. Viral genetic material similar to host cells genetic material Some viral genes are identical to host’s genes 2. Eukaryotic viral genetic material is quite different to prokaryotic and phage genetic material 3. Eukaryotic viral genetic material is similar to transposons (“jumping genes”) Transposons: highly mobile eukaryotic genetic material 2. Phage DNA is similar to Plasmid DNA Plasmid DNA: highly “mobile” extra-chromosomal circular DNA found in bacteria
Lysogenic Conversion Lysogenic Conversion Expression of prophage genes to produce toxins 1. Botulism Bacterium neurotoxin (coded by prophage) paralysis death • Are antibiotics effective against botulism poisoning? 2. Scarlet Fever Bacterium toxin (coded by prophage) sore throat, strawberry-colored tongue, rash death • Give antibiotics within 3 days