Microbiology: The Genetics of Viruses
Viral Genetics Microbiology: The Genetics of Viruses https://www.youtube.com/watch?v=UEKS4w9bfJg Viruses &Bacteria: simplest biological systems
smaller/ simpler than bacteria Contain nucleic acid and protein ONLY Not considered to be living b/c they need a host and NOT make out of a cell Bacteria: larger than viruses Contain ALL marcomolecules considered living Virus Bacterium Animal cell Animal cell nucleus 0.25 m Bacteria with Bacteriophages infecting the cell: What is a virus? Has a genome but
can reproduce only within a host cell Scientists detected viruses indirectly long before they could see them The story of how viruses were discovered begins in the late 1800s: Tobacco mosaic disease stunts growth of tobacco plants gives their leaves a mosaic coloration In late 1800s, researchers hypothesized that a particle smaller than bacteria caused the disease In 1935, Wendell Stanley confirmed this hypothesis Tobacco Mosaic Disease Viruses are not (living) cells!
Viral structure Viruses are not (living) cells! Virus in Latin means poison Made up of infectious particles consisting of a nucleic acid (RNA or DNA) in a protein coat (and sometimes another membrane) Viruses have a Capsid protein shell encloses viral genome (nucleic acid) A capsid can have various structures Viral genomes may consist of Double- or single-stranded DNA (dsDNA, ssDNA) Double- or single-stranded RNA (dsRNA, ssRNA) Viral Structure Images Depending on viral type of nucleic acid
A virus is called a DNA virus or an RNA virus The smallest viruses have only 4 genes, while others have 100s HOST CELL https://www.youtube.com/watch?v=cE0qdqoBFa8 Some viruses have membranous envelopes help them infect hosts
Surround capsids of influenza viruses & other viruses found in animals Viral envelopes (made from host cells membrane) contains a combo of viral and host cell molecules Examples of Viruses and their Hosts
Some viruses have a broad range to infect several species, others infect only a single species West Nile virus can infect mosquitoes, birds, horses and humans Measles virus can infect only humans Most viruses of eukaryotes attack specific tissues Human cold viruses infect only cells lining upper respiratory tract HIV (the virus that causes AIDS) binds only to certain white blood cells (immune cells) General Features of Viral Reproductive Cycles
Viruses are intracellular parasites they can reproduce only within a host cell Each virus has a host range, a limited number of host cells that it can infect Viruses identify host by a lock and key fit between proteins on the outside of the virus and key receptors on the hosts surface Viruses use enzymes, ribosomes, and other HOST molecules to synthesize progeny (offspring) viruses Entry into cell and uncoating of DNA VIRUS LE 18-5 DNA Capsid Replication Transcription HOST CELL Viral DNA mRNA Viral DNA Capsid proteins Self-assembly of new virus particles and their exit from cell Viral infections begin when
Viral genome enters the host cell Once inside, genome takes over its host, reprograms cell to copy viral nucleic acid/manufacture viral proteins instead of host cell needs Host provides nucleotides, ribosomes, tRNAs, amino acids, ATP and other components for making viral components dictated by viral genes Most DNA viruses use DNA polymerases of host cell to synthesize new viral DNA along the templates provided by the viral DNA RNA viruses use special virus-encoded polymerases that can use RNA as a template Once all the parts of the virus are manufactured the virus parts are assembled into new viruses Reproductive Cycles of Phages
Phages = best understood of all viruses Research on phages shows they can reproduce by 2 alternative mechanisms: lytic cycle vs. lysogenic cycle Phages have potential to wipe out bacterial colonies but bacteria also have defenses against them BACTERIRAL DEFENCES INCLUDE: 1. Some bacteria have mutant receptor sites that phage can no longer bind to 2. Bacteria also produce restriction endonucleases, or restriction enzymes, that recognize and cut up foreign DNA, including phage DNA Viral reproduction: Lytic Cycle
A phage reproductive cycle ends in DEATH of host cell Produces new phages and digests the hosts cell wall, releasing the progeny (offspring) viruses A phage that reproduces only by the lytic cycle is called a virulent (strong) phage There are 6 classes A bigger perspective of the Lytic Cycle:
Attachment Entry of phage DNA and degradation of host DNA Phage assembly Release Head Tails Tail fibers Assembly Synthesis of viral genomes and proteins Viral reproduction: Lysogenic Cycle
Replicates the phage genome (DNA)without destroying the host cell Genetic material of virus becomes incorporated into the host cells DNA (called prophage DNA) Every time host divides, phage DNA is copied and passes the copies to the daughter cell The viruses spread without killing the host cells Temperate virus Are phages capable of using the lytic and lysogenic cycles. The term lysogenic implies that prophages are capable of giving rise to active phages that lyse their host cells A bigger perspective of the Lysogenic Cycle:
Phage DNA Daughter cell with prophage The phage attaches to a host cell and injects its DNA. Many cell divisions produce a large population of bacteria infected with the prophage. Phage Phage DNA circularizes Occasionally, a prophage exits the bacterial chromosome, initiating a lytic cycle. Bacterial chromosome Lytic cycle Lysogenic cycle Certain factors determine whether Prophage The bacterium reproduces normally, copying the prophage and transmitting it to daughter cells. The cell lyses, releasing phages. Lysogenic cycle is entered Lytic cycle is induced or Phage DNA integrates into the bacterial chromosomes, becoming a prophage. New phage DNA and proteins are synthesized and assembled into phages. Viral Envelopes Many viruses that infect animals have a membranous envelope Viral glycoproteins on the membrane envelope bind to specific receptor molecules on the surface of a host cell Capsid Capsid and viral genome enter cell RNA HOST CELL Envelope (with glycoproteins) Viral genome (RNA) Template mRNA ER Capsid proteins Glyco- proteins Copy of genome (RNA) New virus RNA viruses = Retroviruses
Retroviruses: transcribe DNA from an RNA template (RNA DNA) These viruses use Reverse transcriptase (catalyzing enzyme) Ex: HIV AIDS Retrovirus (HIV) Viral envelope Glycoprotein Capsid RNA (two identical
strands) Reverse transcriptase RNA viruses mechanisms
The viral DNA that is integrated into a eukaryotic host genome is called a provirus remains a permanent resident of host cell The hosts RNA polymerase transcribes the proviral DNA into RNA molecules The RNA molecules function both as mRNA for synthesis of viral proteins and as genomes for new virus particles released from the cell LE 18-10 HOST CELL Reverse transcription Viral RNA RNA-DNA hybrid
Membrane of white blood cell HIV HOST CELL Reverse transcription Viral RNA RNA-DNA hybrid 0.25 m HIV entering a cell DNA NUCLEUS Provirus Chromosomal DNA RNA genome for the next viral generation mRNA New HIV leaving a cell Retrovirus Animations
Viral Evolution Viruses are intracellular parasites CANT reproduce independently reasonable to assume that viruses evolved after 1st cells appeared Hypothesis for virus origin originate from fragments of cellular nucleic acids that could move from one cell to another original sources of viral genomes? Plasmids (circular pieces of DNA) Transposable elements Combating Viral Infection
Occasionally viral damage can be repaired (ex: respiratory epithelium after a cold) Some infections cause permanent damage (ex: nerve cells after polio) Modern medicine has developed vaccines Vaccines https://www.youtube.com/watch?v=rb7TVW77ZCs Vaccines harmless variants or derivatives (ex: viral proteins) of pathogenic microbes stimulate immune system to mount defenses against actual pathogen (ex: create antibodies) Vaccination has eradicated smallpox Effective vaccines are available against polio, measles, rubella, mumps, hepatitis B, and more Medical Technology cannot
Treat a viral infection that has already occurred (vaccines do not kill viruses) Antibiotics do not treat viral infections Antiviral drugs resemble nucleosides and interfere with the viral nucleic acid synthesis Valtrex stops herpes virus reproduction by inhibiting viral DNA polymerase that synthesizes viral DNA Azidothymidine (AZT) curbs HIV reproduction by interfering with DNA synthesis by reverse transcriptase Currently the most effective treatment is a cocktail multidrug treatment method Emerging Viruses Emerging viruses are those that appear suddenly or suddenly come to the attention of scientists Ex: Severe acute respiratory syndrome (SARS) recently appeared in China Ebola Outbreaks of new viral diseases in humans are usually caused by existing viruses that expand their host territory/range or mutant Recent virus trends HIV appear suddenly in the early 1980s
Each year new strains of influenza are emerging seemingly stronger than previous strains Deadly ebola virus has caused hemorrhagic fevers in central Africa beginning in 1976 West Nile virus appeared for the first time in North America in 1999 Severe acute respiratory syndrome (SARS) appears first in 2003 Avian Influenza (Bird Flu) appears in birds around 1997 and human to human in 2004 (Asia) Young ballet students in Hong Kong wear face masks to
protect themselves from the virus causing SARS. The SARS-causing agent is a coronavirus like this one (colorized TEM), so named for the corona of glyco-protein spikes protruding from the envelope. Where do viruses come from?
About of new human diseases originated in other animals Hantavirus 1993 (mice; SW USA) SARS (exotic animal markets in China) Bird Flu (domesticated chickens, geese, ducks) SIV(Chimpanzees) Changes in host behavior and environmental changes can increase viral infections Destruction of forests and land may bring humans into contact with other animals that may host viruses that can infect us too. Plant Viruses 2,000+ types of known viral diseases of plants
These diseases account for annual loss of $15 billion worldwide Some symptoms are spots on leaves and fruits, stunted growth, and damaged flowers or roots Most are RNA viruses with rod-shaped or polyhedral capsids Plant Viruses spread by 2 major routes
Horizontal transmission Plant is infected with virus by an external source Plants are more susceptible if their protective epidermis (cuticle) is damaged Insects are often carriers Vertical transmission Occurs by asexual propagation or in sexual reproduction via infected seeds Other Pathogens Smaller, less complex things called viroids and prions also cause disease in plants and animals These are DIFFERENT than viruses Viroids tiny, naked circular RNA that infect plants
plant RNA virus w/o capsid do NOT code for proteins, but use cellular enzymes to reproduce stunt plant growth Prions slow-acting, virtually indestructible infectious proteins that cause brain diseases in mammals Prions spread by converting normal proteins into the prion version a transmissible protein Ex: mad cow disease Prions in depth Prions are proteins that spread disease
Appear to cause several degenerative brain diseases scrapie in sheep, mad cow disease, and Creutzfeldt-Jakob disease in humans Likely transmitted in food Have 2 alarming characteristics: VERY slow-acting agents (incubation up to 10 yrs) Virtually indestructible (cannot be destroyed or deactivated by heating to normal cooking temperatures) Prions How can a nonreplicating protein be a transmissable pathogen?
It is a misfolded form of a normal protein When the prion gets into a cell with the normal form of the protein, the prion can convert the normal protein into the prion version, creating a chain reaction that increases their numbers. Small Pox Polio Polio Herpes Simplex Hepatitis Varicella Zoster (chicken pox) Mumps Measles - Rubeola