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Viruses

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Virus associated with cancer. Can be a DNA virus. Adenovirus. Can be a RNA virus. T-cell Leukemia ... Contagious to people who have not had chickenpox, however ... – PowerPoint PPT presentation

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Title: Viruses


1
Viruses
2
What are Viruses?
  • Viruses are pieces of RNA or DNA enclosed in a
    protective coat(s)
  • Viruses are parasites
  • Evolved to reproduce inside cells they infect
  • Evolved to survive outside cells they infect
  • Can do much with little and do it elegantly
  • Hepatitis B is smallest known human virus
  • has only four genes
  • over 1 million people die each year
  • Hepatitis B associated liver disease

3
Structure of Viruses
  • Very small
  • 20-300 nanometers
  • Contain either DNA or RNA (the genome)
  • which codes for the few proteins necessary for
    replication
  • Proteins assembled to form a tight shell capsid
  • Capsid made up of protein subunits called
    capsomeres
  • The of capsomeres is characteristic for a
    particular virus
  • Nucleocapsid genome capsid
  • Some viruses acquire an outer lipoprotein coat by
    budding through host cell membranes enveloped

4
Structure of Viruses (cont.)
  • All viral proteins have reactive epitopes
  • Epitope aka antigenic determinant, part of
    macromolecule (protein) that is recognized by the
    immune system
  • The hosts defense mechanisms
  • Cellular and humoral mediated responses are
    directed against these epitopes
  • Viruses gain entry into host cells by binding to
    specific receptors

5
Specific receptor examples
  • HIV binds to CD4 receptors
  • Can infect cells with these receptors
  • Monocytes, macrophages, T-helper cells
  • EBV (Epstein-Barr) binds to receptor present for
    CR2
  • CR2 Complement receptor type 2 found in B cells
  • Influenza binds to glycophorin A
  • Glycophorin A is found on many cell types
  • Rhinoviruses use ICAM receptors
  • Have the capacity to infect many different cells

6
Replication
  • Adsorption
  • Uptake/Entry
  • Uncoating
  • Genomic activation
  • Assembly
  • Release
  • (animation)

7
3 Problems human viruses must solve
  • How to reproduce
  • How to spread from person to person
  • How to evade host defenses
  • These solutions must fit together in an overall
    plan of infection
  • Wouldnt make sense for a virus that reproduces
    only in liver cells to be spread by coughing
  • It wouldnt do for a virus to evolve to reproduce
    in the intestines, yet not evolve a strategy that
    protects the virus from acidic conditions present
    in the stomach

8
How to reproduce
  • Gain entry to cell via specific receptors
  • Hijack machinery
  • Turn cells into factories that make many copies
    of the virus
  • Make both genome (DNA or RNA) and the proteins
  • DNA viruses use bits and pieces of the cellular
    DNA replication machinery to copy their own
    genomes
  • Problem in cells that are mature and not actively
    replicating their own DNA resting
  • Figure out how to turn infected cell back on
    (give it a kick)
  • Bring its own substitutes for parts of cellular
    copy machines not active at the time of entry

9
How to reproduce (cont.)
  • RNA viruses
  • Bring their own copy machines
  • RNA-dependent RNA polymerases
  • Or have genes which encode the proteins required
    to assemble these copy machines within the
    infected cell
  • By bringing their own many RNA viruses are able
    to replicate their genomes in resting cells
  • animation

10
How to spread
  • Viruses have solved transmission problem in
    ways that take advantage of human behavior as
    varied as coughing or having sex
  • Once it reaches its new host, traveling virus
    must locate cells in which it can reproduce
  • Cell must have appropriate receptors
  • Humans have abut 200 different types of cells a
    given virus usually will be able to infect only a
    few of these many different cell types

11
Viral Pathogenesis
  • Most human viruses cause some form of disease in
    their hosts
  • although some pathological conditions affect only
    a small subset of infected humans, or are so mild
    that they are virtually undetectable.
  • The disease that viruses cause are the
    consequences of the way each virus has chosen to
    solve the problems of reproduction, spread, and
    evasion

12
Viral Pathogenesis (cont.)
  • Viral pathology can result from
  • Actions of the virus itself
  • Killing the cell it infects
  • Hosts reaction to the virus
  • Host immune response
  • Most of the hosts defenses against viruses are
    not finely focused resulting in collateral damage
  • A hosts shotgun approach to defending against
    a viral infection is somewhat like trying to kill
    a mosquito with a machete
  • You may kill that mosquito, but most of the blood
    on the floor will be yours

13
Adsorption
  • Viruses have reactive sites on their surface with
    interact with specific receptors on suitable host
    cells
  • Usually passive (doesnt require E)
  • Specificity of reaction defines and limits the
    host species as well as the type of cell that is
    infected
  • Damage to binding sites (disinfectants, heat) or
    blocking (specific Ab) can render a virus non
    infectious

14
Uptake/Entry
  • After adsorption, uptake/entry can occur in
    different ways
  • the coat of enveloped virus may fuse with host
    cell membrane release the nucleocapsid into
    host cytoplasm
  • Endocytosis-invagination of the cell membrane to
    form vesicles in the cytoplasm

15
Uncoating
  • Release of the viral genome from its protective
    capsid
  • enables the nucleic acid to be transported within
    the cell and transcribed to form new progeny

16
Genomic activation
  • DNA viruses (replicate Io in the nucleus)
  • mRNA is transcribed from viral DNA and codes for
    viral proteins that are translated by host cells
  • RNA viruses (replicate Io in the cytoplasm)
  • Most carry a protein, RNA-dependent RNA
    polymerase which directs both transcription
    replication of viral RNA genome
  • During this process the foreign proteins are
    recognized and incorporated into the major
    histocompatibility complex I molecule (link)
  • Nucleic acid replication produces new viral
    genomes for incorporation into progeny viral
    particles

17
Assembly
  • Assembly of viral nucleocapsids occurs primarily
    in the
  • nucleus
  • For DNA viruses
  • Cytoplasm
  • For RNA viruses

18
Release
  • Final stage of replication
  • Release of new infectious viral particles
    (progeny)
  • May occur by budding-many enveloped viruses
  • Carry with them a piece of hosts cell membrane
  • Lysis (disintegration) of infected cell can also
    release new infectious viral particles

19
Retrovirus
  • contain viral RNA and several copies of reverse
    transcriptase
  • reverse transcriptase (DNA polymerase) is used to
    make the initial copies of viral DNA from viral
    RNA.
  • Once a DNA strand has been synthesized, a
    complementary viral DNA strand is made.
  • These double strand copies of viral DNA are
    inserted into the host-cell chromosome
  • host-cell RNA polymerase is used to make
    virus-related RNA.
  • These RNA strands serve as templates for making
    copies of the viral chromosomal RNA and serve
    also as mRNA.
  • mRNA is translated into viral proteins that are
    used to make the virus envelope.
  • New viral particles are assembled, bud from the
    plasma membrane, and are released.
  • HIV (human immunodeficiency virus) is a retrovirus

20
Oncovirus
  • Virus associated with cancer
  • Can be a DNA virus
  • Adenovirus
  • Can be a RNA virus
  • T-cell Leukemia
  • Oncogenic mechanisms (link)
  • Insert additional oncogenic genes in host DNA or
  • Enhance already exsisting oncogenic genes in the
    genome
  • Viral DNA incorporates a section of the host DNA
    which contains genes for growth promotion
  • Proto-oncogenes

21
Influenza (flu)
  • Infectious disease of birds and mammals caused by
    RNA viruses of the family Orthomyxoviridae
    (influenza virus)
  • Influenza from the latin influentia meaning
    influence (link)
  • Two types that cause epidemic human disease
  • Influenza A
  • Further categorized into subtypes on the basis of
    2 surface antigens
  • Hemagglutinin (H)
  • Neuraminidase (N)
  • Influenza B (not divided into subtypes)

22
Influenza (cont.)
  • New variants result from frequent antigenic
    change aka antigenic drift
  • Results from point mutations that occur during
    viral replication
  • Influenza A gt B (with regard to antigenic drift)
  • A persons immunity to surface antigens (e.g.
    hemagglutinin) reduces
  • Likelihood of infection
  • Severity of disease if infection occurs
  • Antibody (Ab) against one strain confers limited
    or no protection against another strain

23
Epidemics of Influenza
  • development of antigenic variants via antigenic
    drift is the basis for seasonal epidemics
  • Epidemics typically occur during the winter
    months
  • About 36,000 deaths/year in U.S. (1990-1999)
  • Pandemics- dramatic ? in rates of illness/death
  • Due to antigenic shift
  • Morbidity highest among children
  • Mortality highest among elderly (gt 65 years)
    individuals with pre-existing medical conditions

24
Symptoms of Influenza
  • Coryza acute rhinitis
  • Fever
  • Body aches
  • Malaise
  • Generalized muscular aches
  • Loss of appetite
  • A lot of different illnesses can have similar
    symptoms (including common cold)

25
Complications of Influenza
  • Guillain-Barre Syndrome
  • Nerve damage, polio-like paralysis, coma.
    Usually follows recovery from disease or
    immunization to the disease
  • Reyes Syndrome
  • Fever, protracted vomiting, lethargy, sleepy,
    disorientation, incoherence. Liver brain
    damage. Elevation in blood ammonia. High
    mortality. May be associated with aspirin use
    during disease.

26
Vaccine for Influenza
  • Vaccine contains the inactivated virus
  • Several strains of both A and B are included

27
Manual treatment for influenza
  • Some historical perspectives from the osteopathic
    profession.
  • Letter one
  • Letter two

28
Rhinovirus
  • Non-enveloped positive-stranded RNA virus
    belonging to the family picornavirus (pico
    small) along with enteroviruses.
  • Most common viral infective agents in humans
  • cause of common cold
  • Icosahedral (20 faces) in structure
  • Replicate in the secretory mucous membranes
  • Transmission
  • Person to person
  • Via aerosols of respiratory droplets
  • Contaminated surfaces

29
Rhinovirus (cont.)
  • Can lead to (sequelae) but highly unlikely.
  • Secondary bacterial pneumonia
  • Otitis media
  • Sinusitis
  • Prefer lower temperature (33 deg C.)
  • Tend to stay in nose

30
Coronavirus
  • RNA virus belonging to family coronaviridae
  • Cause respiratory infections (common)
  • Enteric infections primarily in infants
    (occasionally)
  • Neurological syndromes (rarely)
  • Transmitted by aerosols of respiratory
    secretions, or by fecal oral route, or by
    mechanical transmission
  • Usually localized to the epithelium of URT

31
Coronavirus (cont.)
  • Most infections cause a mild, self limited
    disease
  • Classical cold
  • SARS (Severe Acute Respiratory Syndrome)
  • Viral pneumonia associated with the LRT
  • Very common worldwide
  • Incidence is seasonal, highest in winter in
    children
  • of serotypes extent of antigenic variation ??

32
Adenovirus
  • DNA virus belonging to family of adenoviruses
  • A few types serve as animal models for cancer
    induction (some are oncogenic)
  • 42 known human serotypes
  • Cause URT or LRT infection
  • Bronchitis (Types 1,2,3,5)
  • Resembles whooping cough-pertussis syndrome
  • Signs
  • Fever, HA, myalgia, pharyngitis, hoarseness,
    conjunctivitis

33
Adenovirus (cont.)
  • Clinical presentation varies based on serotype
  • Bronchitis (1,2,3,5)
  • Sore throat
  • Tonsillitis
  • Conjunctivitis
  • Pneumonia
  • Hepatic disorders (3,7)
  • Gastroenteritis (9,12,13,18,25-28, 40-42)
  • Musculoskeletal disorders (7)
  • Genital infections (19)
  • Skin infections (32, 34-35)

34
Respiratory Syncytial Virus (RSV)
  • negative-sense, single-stranded RNA virus
  • Paramyxovirus Family
  • Family contains viruses that cause mumps
    measles
  • RSV most common cause of bronchiolitis
    pneumonia among infants (lt 1 yr.)
  • Onset fever, runny nose, cough (wheezing)
  • During 1st RSV 25-40 of children have S/S of
    bronchiolitis or pneumonia
  • .5-2 require hospitalization (most lt 6 months)
  • Most recover in 1-2 weeks

35
RSV (cont.)
  • Repeat infections common throughout life
  • Moderate-severe cold symptoms
  • Severe LRT infection may occur
  • esp. in compromised individuals
  • Compromised cardiac, pulmonary or immune systems
  • Spread from respiratory secretions
  • Close contact with infected individuals or
    contaminated surfaces/objects
  • Sneeze/cough (aerosol particles)
  • Route of entry
  • Mucous membranes (eyes, mouth, nose)

36
Metapneumovirus
  • Negative sense RNA virus (paramyxovirus fam.)
  • Discovered in the Netherlands in 2001
  • Very common cause of colds in adults
  • more severe symptoms in children (severe cough
    wheezing)
  • 12 of severe illness
  • 15 of common colds
  • 33 of colds complicated by middle-ear infections
  • Diminished severity in repeat infections
  • Second to RSV as a cause of severe LRTI (2/3)

37
Fifth Disease/Erythema Infectiosum
  • DNA virus-Human Parvovirus B19 (link)
  • Not the same as animal parvovirus (no
    interspecies transfer)
  • Affects primarily children
  • Grows in stem cells, lyses cell to spread
  • Rash produces a slapped cheek appearance
  • Proceeds from face to trunk limbs (like
    measles)
  • Mild systemic respiratory illness
  • Aplastic crisis in individuals with chronic
    anemia
  • Virus infects erythroid precursor cells (reduced
    Hgb)
  • Hydrops fetalis spontaneous abortion as fetus
    infected

38
Varicella (chickenpox)
  • Double stranded DNA virus (Herpesviridae fam.)
  • Prior to mandated vaccine
  • 3.2-4.0 million cases/yr. ? 9000 hospitalizations
    ? 90 deaths (mortality rate 2.25 X 10-5)
  • Among the most communicable of all diseases
  • Transported by respiratory droplets skin
    contact
  • Incubation period 14-21 days
  • Begins in the respiratory tract, symptoms of
    fever, HA, malaise, passes via the blood
    localizing in peripheral nerves skin (fluid
    filled vesicles)

39
Varicella (cont.)
  • Varicella (latin for little vessel)
  • Vesicles form crusts eventually falling off with
    or without a scar
  • Reyes syndrome may occur during recovery (linked
    to aspirin use during illness)
  • Complications (increase with age)
  • Pneumonia, encephalitis, secondary bacterial
    infection of the skin, fetal damage in pregnancy
  • (link)

40
Herpes Zoster/Shingles
  • Caused by the varicella virus that remains in the
    nerve roots after chicken pox
  • Contagious to people who have not had chickenpox,
    however you cannot catch shingles from someone
    else.
  • Common after age 50, risk ?with?age
  • Numbness, itching, severe pain followed by
    clusters of blister-like lesions in strip like
    pattern
  • Pain can persist for weeks, months, or years
    after rash heals ? post-herpetic neuralgia

41
Herpes Zoster/Shingles (cont.)
  • May experience headaches, facial paralysis,
  • One of the more devastating conditions that is
    likely to recur due to
  • physical/emotional stress
  • Suppressed immune system
  • 10-20 of adults will experience at least one
    attack during lifetime

42
Poliomyelitis/Polio
  • RNA-picornaviridae (Greek- gray matter)
  • Three antigenic types
  • Type I/Brunhilde strain
  • Causes a major of epidemics
  • Type II/Lansing strain
  • Occurs sporadically, but invariably paralytic
  • Type III/Leon strain
  • Usually remains in intestines, but can cause
    paralysis
  • Enters body via mouth, multiplies in tonsils,
    then lymphoid tissue of GI tract causing nausea,
    vomiting, cramps

43
Poliomyelitis/Polio (cont.)
  • Virus may pass via blood into the NS, localizing
    in
  • Meninges, causing meningitis
  • Anterior horn, causing muscle weakness, paralysis
  • Brain stem (bulbar), affecting the medulla
    (worst)
  • Difficulty swallowing, paralysis of diaphragm,
    affects breathing (iron lung), paralysis of
    tongue, facial neck ms.
  • Vaccine
  • Salk-killed virus (some viruses could still be
    fxn)
  • Sabin-attenuated (grown in monkey kidney)
  • Sequelae
  • Post polio syndrome (20-30 yrs.) after initial
    infection
  • Muscle weakness

44
Viral Gastroenteritis
  • General name for a common illness occuring in
    both epidemic endemic forms
  • 2nd in freq to common cold in U.S.
  • Usually explosive onset with varying
  • Diarrhea, nausea, vomiting, low grade fever,
    cramps, headache, malaise
  • Can be severe in infants, the elderly, persons
    compromised by other illnesses
  • Associated with
  • Reoviruses, rotoviruses, enteroviruses

45
Reoviruses
  • Double stranded DNA (link)
  • Antigenically 3 human types- orthoreovirus
  • REO respiratory enteric orphan
  • Enters oropharnx replicates in respiratory
    tract intestines
  • Ab against it present in 10 days
  • By age 16
  • 50-80 of population have Ab to all 3 types
  • an orphan is a virus without a famous disease

46
Rotaviruses
  • Most common cause of severe diarrhea among
    children
  • In U.S 55,000 hospitalizations/yr
  • Worldwide 600,000 deaths/yr
  • Incubation period 2 days
  • Vomiting and watery diarrhea for 3-8 days
  • Fever abdominal pain occur frequently
  • Immunity after infection is incomplete, but
    repeat attacks are less severe

47
Rotovirus (cont.)
  • Primary mode of transmission
  • Fecal-oral
  • Virus is stable in environment
  • Transmission via ingestion of contaminated
    food/water, or contact with contaminated surfaces
  • Highest incidence in infants/young children
  • Most children in U.S. infected by 2 yrs.
  • Disease in adults tend to be mild

48
Enteroviruses
  • RNA viruses (picornaviridae)
  • Noroviruses- named after Norwalk virus
  • Four groups divided into at least 20 genetic
    clusters
  • Fecal-oral
  • Highly contagious
  • Incubation 24- 48 hours
  • Acute onset
  • Vomiting, watery diarrhea, abdominal cramps,
    nausea, with occasional low grade fever
  • Dehydration is most common complication
  • Symptoms last 24-60 hours
  • Recovery usually complete with no sequelae

49
Enteroviruses (cont.)
  • Coxsackie virus
  • Two groups
  • A (link)- Associated with diseases with vesicular
    lesions
  • B (body) (link)- Most frequently associated with
    myocarditis and pleurodynia
  • 29 different variants causing a variety of divers
    distinct disease entities
  • Conditions
  • Herpangina- Sores inside the mouth, sore throat
    fever
  • Pleurodynia- Severe pleuritic pain, fever,
    headache
  • Aseptic Meningitis associated with mild paresis
    (transient)
  • Myocardiopathy arrhythmias, tachycardia, can
    cause permanent heart damage
  • Common cold
  • Diabetes Mellitus
  • Hand, Foot, Mouth Disease- rash (vesicles to
    ulcers)

50
Enteroviruses (cont.)
  • Echovirus (link)
  • Enteric Cytopathogenic Human Orphan
  • Occur in many strains
  • Symptoms
  • Gastroenteritis
  • Aseptic meningitis (not associated with bacterial
    infection)
  • Rash
  • Common cold
  • Fairly viable in sewage/water
  • 31 different virus in this group
  • Upper respiratory tract is portal of entry

51
Host Defenses
  • To protect against viral attacks, humans have
    evolved potent defenses
  • Each new host defense has been countered by new
    viral evasion strategies
  • On going struggle between host defenses viral
    counter-defenses even to this day
  • Humans have three types of layered defenses
  • Physical barriers
  • Innate immune system
  • Adaptive immune system

52
Physical Barriers
  • Skin-most difficult barrier for virus to
    penetrate because viruses only infect living
    cells skin has multiple layers of dead cells
  • Respiratory tract- muscosal surface
  • mucociliary elevator preventing viruses from
    getting a grip
  • Macrophages on the loose-phagocytosis

53
Physical Barriers (cont.)
  • Digestive tract
  • Saliva contains compounds active against viruses
  • E.g. secretory leukocyte protease inhibitor
  • Acid conditions of the stomach-pH as low as 2.5
  • Pepsin can break down viral proteins
  • Digestive enzymes in sm. intestine from pancreas
  • Break down CHO, fats, proteins
  • Bile salts from liver (detergents) help break up
    dietary fats viral envelopes

54
Physical Barriers (cont.)
  • Reproductive tract
  • Vagina protected by stratified epithelium
    (multiple layers) of squamous (non-proliferating)
    cells
  • viruses may gain entry via small tears in vagina
  • Mucous that lines the reproductive tract provides
    some protection
  • Normal bacterial flora produce lactic acid
    keeping pH at about 5.0 providing further
    protection against viruses which many are
    sensitive to acidic conditions

55
Innate Defense System
  • Professional Phagocytes
  • Macrophages
  • Phage is Greek to eat therefore big eaters
  • Patrol tissue and collect garbage including
    debris from dead or dying cells
  • Can eat viruses but occasionally can become
    infected by an ingested virus
  • Phagocytes circulating in the blood that can exit
    bloodstream (diapedesis-cross endothelium)
  • Young Macrophages (monocytes)
  • Neutrophils
  • 70 of circulating WBC
  • Provide backup to sentinel macrophages

56
Innate defense system (cont.)
  • Complement System (very old-sea urchins)
  • About 20 different proteins that work together
    to
  • Help destroy invaders signal immune system
  • Proteins produced mainly by the liver
  • Most abundant compliment protein is C3 which is
    continuous broken into two smaller proteins
  • C3a-recruits more macrophages neutrophils
  • C3b-can bind to chemical groups on surface of
    viruses
  • Opsonization-preferred targets for phagocyte
    ingestion-? appetite
  • Binds to enveloped viruses ?membrane attack
    complexes
  • Create holes in protective coat of invading virus
  • One major flaw-only get at viruses outside of
    cells

57
Innate Immune System (cont.)
  • Interferon Warning System
  • Human cells under viral attack produce interferon
    alpha beta (type I interferons)
  • Interferon can be made exported by most cells
    in the body which then bind to receptors on
    surfaces of nearby uninfected cells (warns them)
  • alerts them that they be soon under attack, if
    they are they must commit suicide (apoptosis)
    which limits the spread of the virus
  • Shutdown protein synthesis destruction of RNA
  • The large amount of viral double stranded RNA is
    the trigger for interferon production

58
Innate Defense System (cont.)
  • Natural Killer Cell
  • Specilize in killing virus infected cell that
    dont make class I MHC molecules
  • Kill signal by infected cell
  • Infected cell that does not make class I MHC
    molecules
  • These MHC proteins are used by virus infected
    cells to present viral proteins-alerting killer T
    cells (adaptive) but without class I MHC
    molecules killer T cells are blind to the fact
    the cell is infected, so NK cells pick up the
    slack
  • Cooperation among innate defenses
  • Cytokines (interferon) amp up macrophages
  • TNF (from macrophages) further activate NK cells

59
Adaptive Immune System
  • B cells Antibodies
  • IgM
  • IgG
  • IgA
  • Killer T cells
  • Activation
  • Selection of Weapons
  • Weaknesses-
  • slow to react,
  • must be custom made
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