Unit 5

The Spanish Flu

- 1918 a variant of H1N1 which became known as the "Spanish Flu" infected 1/3 of world's pop (500 million) - the death toll estimated between 30-50 million people

nucleotide

- 5 carbon sugar - deoxyribose on DNA / ribose in RNA - nitrogen-containing base - phosphate group

information flow in most organisms

- DNA > RNA > proteins - but in retroviruses RNA must be converted to DNA before it can be processed by a host cell to produce a protein

genetic material of living things

- DNA only - contains many genes with considerable variation between species (19,000 genes in human genome / 32,000 genes in rice plants genome) - genes contain instructions to produce molecules necessary for cellular function (proteins & RNA)

adenovirus

- DNA virus that has a polyhedral capsid and a fiber at each corner

bacteriophage

- DNA virus that has a polyhedral head and a helical tail

genetic material of viruses

- RNA or DNA - contains a fraction of the # of genes found in living things (only 11 in influenza A) - genes contain instructions for manufacturing the proteins of: the capsid and H/N spikes in the case of influenza A

influenza virus

- RNA virus that has a spherical capsid surrounding by an envelope with spikes

Helper T cells

- T lymphocytes that recognize the antigen attached to the APC at the macrophage's MHC II marker - when they divide, they produce cytokines that alert the antibody-mediated immune response - they also activate cytotoxic T cells

antigenic shift

- a process during which 2 forms of influenza often from 2 different animal hosts infect the same cell - the host may then reassemble them into a new form w/ unique H and N spikes - produces more rapid change in the cirus and delays immune response - can cause widespread outbreaks ex: Spanish flu, Asian flu, Hong Kong flu, H1N1 outbreakF

production of flu vaccinations

- a process that can take up to 6 months

quadrivalent vaccine

- a second form of the vaccine w/ one additional strain: B/Phuket/3073?2013 (Yamagata lineage) virus in 2017-2018, this vaccine contained: 1) A/Michigan/45/2015 (H1N1)pdm09-like virus 2) A/Hong Kong/4801/2014 (H3N2)-like virus 3) B/Brisbane/60/2008-like (B/Victoria lineage) virus 4) B/Phuket/3073/2013 (Yamagata lineage) virus

universal flu vaccine

- a vaccination against influenza that would protect a person from all forms of the virus - might target proteins in the viral capsid that evolve more slowly than the H and N spikes, which are also more similar between viruses

cytokines

- all of the different chemical signals of the immune response - small proteins are usually involved in the localized response to a pathogen (area near an infection or injury) ex: - histamine: increase capillary permeability; causes fluid to be released in the area of a wound - interferon: signals other nearby cells when a cell has been infected by a virus - interleukin: glycoprotein that helps regulate the general immune response

viral structure attachements

- assist the virus in attaching to its host - tail fibers + spikes

influenza virus

- causes the flu - an RNA virus surrounded by a capsid and an envelope - has spikes on the surface (glycoproteins - a protein with a sugar attached) that assist the virus in identifying and entering its host cell - four forms (A, B, C, D) A and B most prevalent

evolution at all levels of bio

- cellular level: the evolution of cells including how plant cells evolved to photosynthesize - organism level: the internal physiology of individual organisms - ecosystem level: interactions of ecosystems such as rain forests and coral reefs

evolution

- changes in species or population over time - one of the fundamental concepts in the study of biology (almost every aspect of the biological sciences may be explained by evolutionary processes - biologists study evolution as it relates to human evolution, antibiotic and insecticide resistance, how diseases develop over time - the study of mechanisms for evolutionary change over time has resulted in the production of better medications including vaccines and antiviral agents

cytotoxic T cells

- clones of the helper T cells - specialized T lymphocytes that cause apoptosis in the infected target cell - recognize targets by their antigens, bind to them directly and destroy them - they release a protein (perforin) that opens a holes in the target cell membrane, allowing molecules called granzymes to enter and force the cell to undergo apoptosis

nasal spray vaccine

- contains weakened versions of flu viruses - may produce some flu-like symptoms - its effectiveness especially against swine flu (H1N1) is debated - not recommended for use by CDC in 2017/2018

variation

- differences in traits - exists within the genotypes of populations - natural selection acts on the variation within a population by favoring some variants over others - ensures a population will not go extinct - is beneficial b/c populations w/ limited variation may not be able to adapt to new condition if environment changed

how are vaccines produced

- egg method (uses fertilized chicken eggs) - cell based method (uses mammalian cell cultures) - recombinant process (uses H spikes added to a virus that infects cells

genetic material 2

- either DNA or RNA - a nucleic acid that stores genetic info and contains a set of instructions called genes - DNA (double stranded) whereas RNA (single stranded) - in living things genes have all info for cell to produce the proteins and RNA it needs to function

tail fibers

- fiber proteins - found on surface of adenovirus

physical evidence of evolution

- fossils - comparative anatomy of living organisms - analogous structures: structures that serve the same function that evolved independently (ex: wings of birds/bats/insects) - homologous structures: structures that are similar b/c they are inherited from a common ancestor (ex: bone structure of limbs in mouse, bat, and whale) - embryonic development: similarities among embryos of different species

vaccinations

- generate active immunity by exposing individuals to antigens specific to pathogens - vaccinations against the flu use viral spikes as antigen - a primary response is mounted and memory B and T cells are produced by the immune system - often, a second vaccination is required and the body mounts a secondary response that increases the production of memory B and T cells

molecular evidence for evolution

- genetic material: comparison of the DNA, genes, and proteins of different species (protein sequences, DNA sequences, cytochrome c [protein], Hox genes [developmental genes])

how are viruses selected

- global influenza samples are reviewed for potential to cause a worldwide pandemic, what is known about each strain, and their ability to produce an effective vaccine against each strain

spikes

- glycoproteins - found on surface of influenza A virus - the name of each influenza A strain includes the type of spikes present

influenza viruses are named based on:

- host: if host is non-human it is included in the name, if human, not included - type (A or B) - location first isolated - strain # - year first isolated - types of spikes (influenza A) - lineage designation (influenza B) to identify viral history ex: A / Michigan / 45 / 2015 / (H1N1) pdm09-like virus

RNA viruses and diseases

- human immunodeficiency virus (HIV) (AIDS) - influenza viruses - poliovirus - measles virus - rabies virus - ebola virus - west nile virus - rhinovirus (common cold) - hepatitis A and C viruses - zika virus

examples of antigenic shift in influenza virus

- involves animal host - when 2 different forms of influenza infect the same host (ex. pig) and the host cells manufactures viral particles from both forms - when new viruses are assembled they have characteristics of both forms on the same new virus

immune system

- is responsible for protecting the human body from pathogens - immune cells interact w/ tissue + organs of the body where they may destroy pathogens + infected cells, produce antibodies, target infected cells - remembers exposure to past pathogens like the flu so that it may respond faster upon re-exposure - monitors lymph fluids for the presence of pathogens

protective proteins

- known as complement (a group of serum) proteins - enhance inflammation, lyse cells, and act as molecular tags that identify pathogens for destruction - can destroy bacterial cells by creating holes in the cell's membrane - act in a cascade and can be activated by several foreign molecules, such as an antigen-antibody complex on the surface of a pathogen or free antigens in the body fluids

antibodies

- large protein molecules that bind to a specific antigen - can clump together around and antigen to inactivate it - can bind to antigen and flag it for destruction by a natural killer cell (promote interaction of natural killer cells w/ the antigen)

antigen-presenting cells (APCs)

- macrophages that are displaying the antigen of the invading pathogen they have digested

antiviral medicines

- medications that target the viral life cycle 3 common examples: - tamiflu - rapivab - relenza all 3 inhibit the enzyme neuraminidase which allows influenza to exit the host cell

how influenza targets its host

- most viruses are specific about the type of cells they infect and target these cells with their capsid proteins which are specific to the molecules on the surface of the target cell - the complex 3D shapes of capsid proteins complement the host cell receptor - influenza A targets host cells using its H spikes which identify a glycoprotein receptor embedded in the host cell membrane

examples of antigenic drift in influenza virus

- mutations (that occur during viral reproduction) can result in modified spikes which create novel strains of the flu

DNA viruses + diseases

- poxvirus (smallpox) - herpesviruses (chickenpox, oral herpes, genital herpes) - hepatitis B - papillomaviruses (cervical cancer, genital warts) - epstein-barr (mononucleosis, burkitt lymphoma)

B cells

- produced in red bone marrow - mature in red bone marrow - involved in antibody-mediated immunity - differentiate into antibody-screening plasma cells - once activated , undergo clonal selection

T cells

- produced in red bone marrow - mature in thymus - involved in cell-mediated immunity - activated anywhere in body where antigen is presented by MHC proteins - bind to antigens processed and presented by MHC proteins - include helper and cytotoxic cells - once activated, undergo clonal selection - contain antigen receptors

lymphatic system

- returns fluids, called lymph, from the tissues to the circulatory system - filters and cleans the blood and interstitial fluids of the body - produces immune cells - site of maturation of immune cells - includes: red bone marrow, thymus, lymph nodes, spleen, lymphatic vessels

adaptive immunity

- specific and targeted immunity, unlike the innate defenses; has ability to remember past immune responses - targets antigens associated w/ a specific pathogen in a cell or body fluid 2 forms: 1) (antigens within cells) cell-mediated immunity: targets infected body cells with white blood cells called T lymphocytes; results in phagocytosis or apoptosis of infected cells in response to a specific antigen 2) (antigens outside cells) antibody-mediated immunity: targets antigens outside cells, in the blood or body fluids, using white blood called B lymphocytes; results in production of plasma cells and antibodies in response to a specific antigen

1st line of defense (physical barriers to entry)

- structures and chemicals that slow pathogens and prevent them from entering the body - ex: skin (bacteria on the surface and chemicals released by glands inhibit bacterial growth), respiratory tract (mucous membranes trap microbes and also contain chemicals that protect against pathogens; cilia), stomach (hydrochloric acid destroys bacteria and other pathogens)

Alfred Russel Wallace

- studied biogeography in S. Pacififc islands - observations lead him to propose concept of speciation: how changes in a population over time can lead to the formation of a new species - shared work w/ Darwin who recognized the significance of the parallel discoveries + incorporated both their ideas into book (On the Origin of Species 1859)

Charles Darwin

- studies fossils & biogeography on west coast of S. America and in the Galápagos islands in the Pacific Ocean - discoveres similar environments in S. America and Europe had animals w/ similar appearances - noted variation in animals on each island in the Galapagos: finches had varying beak size, food source differed on each island he proposed: the idea of descent w/ modification + the process of natural selection

antigens

- substances that are specific to pathogens and that produce specific immune responses in the body

antiviral medicines that target specific stages of the viral life cycle

- targeted during attachment stage: medicine targets the molecules on the surface of the host cell or proteins that the virus uses to attach to the cell - targeted during uncoating stage: medicine inhibits the enzyme that allows the virus to release its genetic material from the viral capsid - targeted during release stage: medicine inhibits the viral enzyme neuraminidase, which is what allows the virus to leave the host cell

innate immune defenses

- the general, nonspecific, immune defense against bacteria, viruses, and other pathogens

2nd line of defense (protective proteins)

- the immune system produces a variety of protective proteins known as complement proteins - these molecules: act as molecular tags, identify pathogens for destruction by the immune system

protecting the body from pathogens

- the immune system works closely w/ the lymphatic system to protect the body from pathogens - the coordinate of these systems involves immune cells and lymphatic tissues and fluids

major-histocompatability complexes

- the immune system's ability to distinguish self from non-self involves two different forms of plasma membrane glycoproteins, both of which are called major-histocompatability complexes (MHCs) 1) MHC class I markers (MHC-I) are present on all nucleated body cells and serve as "self" indentification tags 2) MHC class I markers (MHC-II) are present on some immune cells and are important in initiating immune responses

trivalent vaccine

- the most common vaccine which contains 3 strains of the virus - in 2017-2018 this vaccine contained 1) A/Michigan/45/2015 (H1N1)pdm09-like virus 2) A/Hong Kong/4801/2014 (H3N2(-like virus 3) B/Brisbane/60/2008-like (B/Victoria)

envelope

- the remnants of the plasma membrane of the host cell - does not function to regulate movement of materials in and out of the virus - assists the attachment and entry of the virus into a host - surrounds the capsid

lysogenic cycle

- the virus integrates directly into the host cell genome and delays its own reproduction - allows a virus to become inactive (latent) in the host cell until environmental factors signal it to re-enter the lytic cycle ex: HIV

influenza infects epithelial cells

- throughout body epithelial cells form thin layer of tissue called epithelium that is often only one cell layer thick; this tissue forms the boundary between the body's tissues and the external environment - the primary target of influenza virus is the epithelial cells that line the respiratory system - b/c substances that enter or leave the blood or body tissues must first pass through the epithelial cells which play a vital role in regulating activities within body - when influenza invades the epithelial cells, normal cell function is disrupted, which accounts for many of the flu symptoms - as the epithelial cells lose their function they may undergo apoptosis (programmed cell death)

types of flu vaccinations

- two forms of the injectable flu vaccine and 1 nasal spray vaccine produced each year - in both injectables the viral particles are inactivated (killed) and are not capable of reproduction (one injectable contains 3 strains of the virus and the other contains 4)

B lymphocytes 2

- while the T cells of cell-mediated immunity work to target infected cells, B lymphocytes begin to produce antibodies - each B lymphocyte can produce a single form of antibody for one specific antigen - w/in each B cell there are genes that allow the lymphocyte to produce antibodies that vary slightly in their structure - if a B cell recognizes an antigen, it can start to produce antibodies against it - helper T cells can activate B cells creating plasma cells that divide rapidly to produce clone B cells that produce antibodies (clone expansion)

phagocytes and natural killer cells

- white blood cells help to fight infection by attacking invading microbes - phagocytes: identify pathogens and destroy them by phagocytosis (ingesting and digesting them) ex: macrophages - engulf and digest pathogens one at a time neutrophils - engulf microorganisms and release chemicals that kill nearby bacteria (and themselves) (neutrophils may release cytokines to recruit more immune cells) - natural killer cells: puncture the membrane of infected target cells w/ a molecule called perforin, which forms a pore that allows water to rush in perforins are secreted by T cytotoxic cells and function by making a hole in the membrane of targeted cells

T lymphocytes 2

- white blood cells produced in bone marrow that mature in the thymus - when mature, they develop receptors for a single form of antigen

cell-mediated immunity

-targets infected cells that are presenting the antigen for the pathogen they are infected with

evolution of whales

1) Ambulocetus - terrestrial ancestors that walked on 4 limbs 2) Basilosaurus - gradual reduction in hind limb + shift of nasal openings to top if head 3) Right whale - remnants of a hindlimb

lytic cycle process

1) attachment - capsid combines w/ receptor 2) penetration - viral DNA enters the host 3) biosynthesis - viral components are synthesized (put inside host) 4)maturation - viral components are assembled (inside host) 5) release - new viruses leave host cell

viral life cycle

1) attachment: the stage during which a virus attaches to a target host cell based on the proteins in the viral capsid, which recognize host cell receptors 2) uncoating: a stage at which some viruses, once inside host cell, provide an enzyme to remove their genetic material from its viral capsid 3) release: the stage at which new viral particles exit the host cell; the virus may exit via the host cell plasma membrane (exocytosis) or the host cell may burst (cell lysis)

the path of influenza through the body

1) can enter respiratory system through mouth or nose 2) pharynx 3) trachea + lungs 4) alveoli (location of gas exchange) are lined with a single layer of epithelial cells once in respiratory tract - H spikes identify host epithelial cells by detecting glycoproteins on the surface - N spikes break down the membranes of the epithelial cells and start process of entering host cell the replication cycle (lytic cycle) begins almost immediately as the virus: - takes over the host cell's machinery to make new viruses - produces proteins that interfere w/ normal function of the epithelial cells some epithelial cells lose function while others die causing inflamed tissue

influenza evolution

1) each strain of the influenza virus has unique H and N spikes on surface 2) mutations can occur during viral reproduction 3) mutations can result in modified spikes, which create novel strains of the flu another mechanisms of influenza evolution involves an animal host - 2 different forms of influenza infect the same animal host, and the host cells manufacture viral particles from both forms; when new viruses are assembled, they have characteristics of both forms on the same new virus (antigenic shift) - antigenic drift is caused when mutations alter the viral spikes

natural selection

1) individuals vary in their traits (individual organisms within a species exhibit variation that can be passed from one gen to the next) 2) individuals struggle to exist (organisms compete for available resources) 3) individuals differ in the fitness (individual organisms within a population differ in terms of their ability to compete for resources, survive, and reproduce) 4) populations become adapted to the environment (organisms become adapted to conditions as the environment changes)

evidence for natural selection

Darwin developed theory of evolution by natural selection based on observations made while serving as naturalist on the HMS Beagle for 5 yrs - galapagos finches on each island had similar overall appearance but variation in their beak size and shape - ground dwelling finch has heavy beak for its diet of large seeds - warbler-finch beak has short for feeding on insects in plants or in air - cactus finch has longer curved break and split tongue for extracting flesh of cactus fruit - Darwin also noted similarities between species living on separate continents ex: african ostrich and s. american rhea

when are viruses selected

February prior to start of flu season (northern hemisphere) and September prior to start of flu season (southern hemisphere)

genetic material

RNA or DNA which, in viruses, contains only a small number of genes

thimersol

a preservative that may be present in some multi-dose vials of the vaccine

capsid

a protein coat surrounding the genetic material

antigen

a substance that prompts an immune response

virus

an obligate intracellular parasite that hijacks the metabolic machinery of a host cell to replicate itself - viruses are sometimes called obligate intracellular parasites meaning they require a host cell to make copies of themselves - not historically classified as living organisms

antigenic organism

an organism that can evade the immune system

fossils

any past evidence of an organism that has been preserved in the Earth's crust - mineralized remains - shell, skeleton, teeth are left behind and mineralized - majority are found embedded in sedimentary rock - when arranged from oldest to youngest they can provide evidence of evolutionary change

adaptive responses

are activated when: - a macrophage engulfs and digests a pathogen and then displays an antigen (specific to that pathogen) on its surface (this antigen-presenting macrophage is called an APC, or antigen-presenting cell) - then, a lymphocyte called helper T cell recognize the combination of MHC-II and the antigen on the surface of the macrophage

individual and population level risk

b/c the immune system recognizes influenza's H spikes as antigens, changes in the viral structure create risk at the individual and population level

comparative anatomy

comparison of physical characteristics - analogous homologous

cause of flu symptoms 2

cytokines: (chemical signals) proteins released by white blood cells to alert organs of the presence of a pathogen different ways cytokines affect body systems: - digestive (symptoms: loss of appetite, nauseas, vomiting) cytokines that reduce the action of appetite centers in brain - muscular (symptoms: joint and muscle aches) cytokines that break down muscle fibers and cause fluid to accumulate in the tissue - nervous (symptoms: headache, fever) cytokines that signal the hypothalamus to raise body temp. - integumentary (symptoms: chills) cytokines that restrict blood vessels in the skin to conserve heat

Bacteria

domain that includes cyanobacteriaand herterotrophic bacteria

Eukarya

domain that includes plants, animals, fungi, protists

Archae

domain that includes single-celled prokaryotes

aluminum salts

enhance ability of immune system to detect virus (some vaccines are aluminum-free)

disruptive selection

favors both extreme variations selecting against the most common variant - produces a divide in the distribution curve resulting in 2 distinctly differe t phenotypes

directional selection

favors one extreme for a trait - shift in the distribution of phenotypes to favor an extreme ex: antibiotic resistance

stabilizing selection

favors the most common variant for a trait - extreme pheotypes are eliminated and the average phenotype is conserved ex: human birth weight

natural killer (NK) cell

function: destroy cells of the body that have been infected by viruses or bacteria (nonspecific)

macrophages, dendritic cells, + neutrophils

function: destroy pathogens by phagocytosis (nonspecific)

B lymphocytes

function: produce antibodies to target specific antigens in the fluids of the body (specific)

T lymphocytes

function: targets cells that have been infected by a specific pathogen (specific)

H spikes

hemagglutinin glycoproteins that assist virus in identifying receptors on the host cell - 17 different known forms

genetics

how genetic material changes over time

ecology

how organisms habe evolved to fill their roles within the ecosystems

evolution driven by genetic changes

in order for a species to evolve, changes must be passed from one generation to the next so they must occur at the DNA level - some changes can result in species becoming more adapted to environment - can take millions of years for evolution to produce detectable changes in a species - viruses reproduce more quickly ex: human influenza originate in animals and evolve into new forms that can infect humans

how genetic material changes

in order for evolution to occur 1) there must be a variant for a trait within a population 2) the variant must be passed to next gen the info for traits is contained within pattern of nucleotides in DNA the genetic material (DNA or RNA) is a nucleic acid that stores genetic information + containes a set of instructions called genes for specific traits proteins are everything form the enzyme in chemical reaction to traits, like eye color humans can produce 100s of 1000s of proteins from less than 20,000 genes

formaldehyde

inactivates any toxins from the viruses or bacteria that may have been present during production

examples of epithelial tissue

lining the - nose, mouth + esophagus - trachea - lungs - blood vessels - small intestines

N spikes

neuraminidase enzyme that helps break down the mucous material surrounding host cells in the respiratory tract and begin the process of penetration of the virus into the host cell - 10 different known forms

innate immunity

nonspecific, general defense mechanism - does not target a specific pathogen ex: barriers to entry, protective proteins, phagocytes + natural killer cells, inflammatory response

viral reproduction

once a virus has entered a host cell there are 2 general pathways it can follow to reproduce both of which hijack the host cell machinery in order to produce copies of the virus

antibiotics

prevents bacterial growth during preparation and storage of vaccine

egg protein

remnants from the production of the vaccine - newer vaccines do not use eggs and do not contain these proteins

cause of flu symptoms

respiratory symptoms are caused by the virus itself, which produces proteins that interfere w/ the function of epithelial cells, interfering w/ tissue function which causes - congestion + trouble breathing when fluid accumulates in lungs - sore throat when epithelial cells become inflamed some respiratory symptoms are result of immune response to the virus which produces a lot of mucus - immune response increases blood flow and deploys immune cells to respiratory tissue creating mucus (excess mucus can trap the virus helping body expel it through coughing + sneezing)

transitional fossils

serve as a link between groups ex: Archaeopteryx, lived 165 mil yrs ago, had characteristics of dinosaurs (long, jointed tail, jaws w/ teeth) and birds (feathers, wings)

all viruses have:

similar structure but vary in shape and form of genetic material - genetic material - a capsid

cytochrome c

small protein that plays an important role in the electron transport chain within mitochondria of all cells - a common ancestor at 50 amino acids branches out to 8 species (yeast, moth, fish, turtle, duck, pig, monkey, human)

gelatin, sorbitol, or monosodium glutamate (MSG)

stabilize the vaccine and protect it from temperature variations during storage

homologous

structures that are both similar in a appearance and structures b/c they have been inherited from a common ancestor ex: bone structure of limbs of mouse, bat, whale

analogous structures

structures that serve the same function and often appear the same but evolved independently as adaptations to a specific environment ex: the wings of an insect and bird

systematics

studies evolutionary relationships of organisms; helps to organize them into groups

fitness

the ability of an organisms to reproduce and pass it genes to next fertile gen - is measured against ability of other organisms to reproduce in the same environment + by the # of fertile offspring produced during an organisms lifetime

immune recognition of "self" and "non-self"

the challenge of protecting the trillions of cells in the human body requires the immune system to be able to recognize cells that do not belong to the body - a series of markers on the plasma membrane of each cell help with this task; these molecules are glycoproteins - proteins w/ sugar groups attached

biochemical unity

the closer the genetic info os between 2 species, the closer their evolutionary relationship - the closer 2 organisms are evolutionarily, the less time has passed to change the genetic info - influenza can be examined this way; comparing RNA sequence between strains over time can help scientists to observe genetic changes in the virus

inflammatory response

the first action taken by the immune system when the body is injured 1) - damaged tissues release chemical alarm signals called histamine - the capillaries leak fluid that slows pathogen movement - blood flow is increased to the area of the injury to deliver white blood cells and clotting factors 2) - macrophages identify and destroy bacteria or viruses in the vicinity of the wound - neutrophils remove dead cells, wound debris, and pathogens by phagocytosis - depending on the severity of the injury, neutrophils may release cytokines to recruit more immune cells 3) - monocytes, which are a type of white blood cell, become macrophages and engulf pathogens and remaining dead cells - eventually clotting factors close off the wound, causing pressure to build - this account for the red, tender appearance of inflamed tissue

biology

the study of the natural world

lytic cycle

the virus immediately uses its host cell's resources to create copies of itself ex: Influenza A

what's in a vaccine

vaccines contain inactivated or weakened viruses and additives to preserve the vaccine's contents

antigenic drift

when a mutation is introduced into the genetic material of the influenza virus, it can change the viral spikes - when a host cell is used to reproduce the virus, mRNA is synthesized directly from virus RNA (by RNA polymerase) - when RNA polymerase makes an error there's a mutation which allows the virus to evolve rapidly - a mutated form of influenza is less recognizable to immune system thus this modification can make the annual vaccine less effective - causes more local outbreaks