Ch 6, 25, 26 Flashcards

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1
Q

Louis Pasteur

A

Postulated that rabies was caused by a “living thing” smaller than bacteria

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2
Q

Dimitri Ivanoski

A

First proposed the term “virus” - poison

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3
Q

Ivanoski and Beijerinck

A

Showed a disease in tobacco was caused by a virus

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4
Q

Viruses

A
  • Noncellular particles with a definite size, shape, and chemical composition
  • there is no universal agreement on how and when viruses originated - likely multiple origins
  • considered the most abundant microbes on earth
  • infect all domains of life
  • viruses played a role in the evolution of bacteria, archaea, eukarya
  • obligate intracellular parasites
  • not alive
  • lack enzymes for most metabolic processes
  • lack machinery for synthesizing proteins
  • does not consist of one or more cells
  • rely on host and and can’t do things independently, like replicate, process, or metabolize
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5
Q

Virus size

A
  • ultramicroscopic - less than 0.2 micrometers; require electron microscope
  • largest viruses average around 500-1,000 nanometers (mega viruses and panda viruses), which is 20-50x larger than an average virus
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6
Q

Virus Shape

A
  • some viruses have an external covering, an envelope; those lacking an envelope are naked
  • all have capsids (protein coats that enclose and protect their nucleic acid; each capsid is made of identical protein subunits called capsomers
  • the capsid together with the nucleic acid (DNA or RNA) is the nucleocapsid
    *shape is determined by the nucleocapsid
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7
Q

Two structural capsid types

A
  1. Helical: continuous helical of capsomers forming a cylindrical nucleocapsid
  2. Icosahedral: three dimensional, symmetrical polygon, with 20 sides and 12 evenly spaced corners
    *complex/irregular: those that “don’t follow the rules”
    - regular shapes often lead to aggregate/crystal formation
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8
Q

Helical Capsids

A

Nucleocapsid Assembly:
- rod-shaped capsomers assemble into hollow discs
- the nucleic acid is inserted into the center of the disc
- elongation of the nucleocapsid progress from both ends, as the nucleic acid is coiled inside

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9
Q

Icosahedral Capsid

A

Icosahedral: three-dimensional, symmetrical polygon, with 20 sides and 12 evenly spaced coroners
- arrangements of capsomers vary among Icosahedral viruses
- they can also vary in number of capsomers
- during assembly of the virus, the nucleic acid is packed into the center of the icosahedron, forming the nucleocapsid
- they can be enveloped or naked
A) Rotavirus (naked)
B) Herpes simple (enveloped)

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10
Q

Structure of Complex/Irregular Virus

A

Atypical Viruses
- Poxviruses: lack a typical capsid and are covered by a dense layer of lipoproteins
- Some bacteriophages have a polyhedral nucleocapsid along with a helical tail and attachment fibers

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11
Q

General Structure of Envelope Viruses

A
  • mostly in animal viruses
  • acquired when the virus leaves the host cell (source varies)
  • exposed proteins on the outside of the envelope], called spikes, are essential for attachment of the virus to the host cell
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12
Q

Functions of capsid/envelope

A
  • protects the nucleic acid when the virus is outside of the host cell
  • helps the virus bind to a cell surface and assists the penetration of the viral DNA or RNA into a suitable host cell
  • capsids are “metastable” structures
  • disruption of external structures renders particle non-infectious
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13
Q

Viral Genome

A
  • either DNA or RNA
  • carries genes necessary to invade host cell and redirect cells activity to make new viruses
  • number of genes varies for each type of virus - few to hundreds
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14
Q

DNA Viruses

A
  • usually double stranded but may be single stranded
  • circular or linear
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15
Q

RNA Viruses

A
  • usually single stranded, may be double stranded, may be segmented into separate RNA pieces
  • ssRNA genomes ready for immediate translation are positive-sense RNA
  • ssRNA genomes that must be converted into proper from are negative-sense RNA
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16
Q

Other substances packaged in viruses

A

Pre-formed enzymes generally required for viral replication
- Polymerases: synthesize DNA or RNA
- Replicases: copy RNA
- Reverse transcriptase: synthesis of DNA from DNA (HIV virus)
*matrix protein enzymes (not found in all viruses)

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17
Q

Virion

A

Complete Infectious Particle
- consists of covering: capsid & envelope (not found in all viruses)
- consists of central core: nucleic acid molecules (DNA or RNA) & matrix protein enzymes (not found in all viruses)

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18
Q

Virus Classification

A

Classification based on numerous characteristics
- nucleic acid type
- presence or absence of envelope
- capsid symmetry
- dimension of virion and capsid

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19
Q

Virus Taxonomy and Phylogeny

A
  • lack of information on origin and evolutionary history makes viral classification difficult
  • a uniform classification system developed in 1971 by the international committee for taxonomy of viruses (ICTV); most current report 2,00 viruses, 6 orders, 87 families, 19 subfamilies, and 349 genera
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20
Q

Alternative Classification Scheme

A

David Baltimore (focuses on viral genome and process used to synthesize viral mRNA
- 7 life cycles groups based on:
- double stranded DNA
- single stranded DNA
- double stranded RNA
- single stranded RNA (+ or -)
- retrovirus

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21
Q

Viral Replication

A
  1. Adsorption: attachment to the host
  2. Penetration/Uncoding - entry of genome into the host
    A. Get genome into host cell
    B. Deliver to specific location in the cell
  3. Synthesis: using the host to make viral proteins and nucleic acids
    A. Copy genome
    B. Make viral proteins
  4. Assembly/Maturation: assembly of new virons
  5. Release: various consequences to host cell
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22
Q

Review of Transduction/Bacteriophage Replication

A
  • Adsorption and Penetration: phage is adsorbed to receptor site on bacterial cell wall, penetrates it, and inserts its DNA
  • Biosynthesis: the phage DNA directs the cell’s metabolism to produce viral components proteins and copies of phage DNA
  • Maturation: heads are packed with DNA
  • Release: bacterial cell lyses, releasing completed infective phages
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23
Q

Viral Specificity

A
  • Defined by whether a virus can attach to a cell
  • Requires two things
    1. A receptor on the host cell
    2. A protein on the virus that recognized and attaches to the receptor
    *This will define the tropism of a virus
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24
Q

Process of the Penetration/Uncoating

A
  • entry of genome into the host
    A. Get genome into host cell
    B. Deliver to specific location in the cell (DNA - nucleus) or (RNA - cytosol)
  • most viruses enter through one of two means
  • fusion: (envelope viruses) - viral envelope fuses directly with host membrane by rearrangement of lipids
  • endocytosis: (enveloped or naked) - entire virus is engulfed and enclosed in a vacuole or vesicle. Once inside, the virus is uncoated and viral nucleocapsid or nucleic acid is released
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25
Q

Process of synthesis

A

Using to make viral proteins and nucleic acids
A. Copy Genome
B. Make viral proteins
- varies depending on whether the virus is a DNA or RNA virus
- DNA viruses generally are replicated and assembled in the nucleus - often use host enzymes
- RNA viruses generally are replicated and assembled in the cytoplasm - often use viral enzymes; RdRp = RNA-dependent RNA polymerase - must make or bring with it
- positive-sense RNA contain the message for translation
- negative-sense RNA must be converted into positive-sense message

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26
Q

Process of release

A

Various consequences to host cell; chronic release (budding or exocytosis)
Or lysis/cell death

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27
Q

Persistent Infections

A
  • cell harbors the virus and is not immediately lysed
  • can last weeks or host’s lifetime; several can periodically reactivate
  • chronic latent state
  • some animal viruses enter the host cell and permanently alter its genetic material, resulting in cancer
  • these viruses are termed oncogenic, and their effect on the cell is called transformation
  • transformed cells have an increased rate of growth, alterations in chromosomes, and the capacity to divide for indefinite time periods resulting in tumors
  • mammalian viruses capable of initiating tumors are called oncoviruses
  • papilloma virus - cervical cancer
  • Epstein-Barr virus - Burkitt’s lymphoma
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28
Q

Observable changes/damage in virally infected cells

A

Cytopathic effects: cell damage altering microscopic appearance
- disorientation of individual cells
- gross changes in shape or size
- intracellular changes (inclusion bodies, syncytium)

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29
Q

Cytopathic changes in specific viruses

A
  • smallpox:cells round up; inclusions appear in cytoplasm
  • herpes simplex: cells fuse to form multi nucleated syncytia; nuclear inclusions
  • adenovirus: clumping of cells; nuclear inclusions
  • poliovirus: cell lysis; no inclusions
  • renovirus: cell enlargement; vacuoles and inclusions in cytoplasm
  • influenza virus: cells round up; no inclusions
  • rabies virus: no change in cell shape; cytoplasmic inclusions (Negri bodies)
  • measles virus: syncytia form (multinucleate)
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30
Q

Medical importance of viruses

A
  • viruses are the most common cause of acute infections
  • several billion viral infections per year
  • some viruses have high mortality rates
  • possible connection of viruses to chronic afflictions of unknown cause
  • viruses are major participants in the earth’s ecosystem
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31
Q

Detection and treatment of animal viral infections

A
  • more difficult than other agents
  • consider overall clinical picture
  • take appropriate sample
  • infect cell culture - look for characteristic Cytopathic effects
  • screen for parts of the virus
  • screen for immune response to virus (antibodies)
  • antiviral drugs can cause serious side effects
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32
Q

Extra take home messages

A
  • viruses are very different from other infectious agents
  • to truly understand them, you need a very firm grasp on the basics of DNA structure and replication, RNA transcription, and protein translation process
  • the trick with each type is to ask what is the shortest set of cellular events to get from the viral genome inserted into the cell to newly-made virus particles
  • events for each group of viruses will come in handy when thinking about how to interrupt these cycles with antiviral drugs
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33
Q

Parvoviruses

A
  • non-enveloped, ssDNA
  • primarily transmitted via direct/indirect contact
  • small diameter and genome size
  • causes distemper in cats, enteric disease in dogs, fatal cardiac infection in puppies
  • few cause infections in humans
    B19 cause of erythema infectiosum (fifth disease); rash of childhood
  • children may have fever and rash on cheeks (-slap-face-rash)
  • severe fatal anemia can result if pregnant woman transmits virus to fetus (low but know risk)
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34
Q

Human Papillomavirus

A

Papilloma: squamous epithelial growth, wart, or verruca
- cause by 100 different strains of HPV
- transmissible through direct contact or contaminated fomites; incubation - 2 weeks to more than a year
- most common warts regress over time; they can be removed by direct chemical application of podophyllin and physical removal by cauterization, freezing, or laser surgery
- warts can recur
- warts described by location
- common seed warts: painless, elevated rough growth; on fingers, etc
- plantar warts: deep, painful; on soles of feet
- genital warts: most common STD in US, morphology ranges from tiny, flat, inconspicuous bumps to extensive, branching, cauliflower-like masses
- warts are good at causing uncontrolled growth of cells and avoiding immune recognition
- ten HPV types increase risk for developing reproductive cancer; 2 (HPV16 and HPV 18) account for 70% for metastatic tumors
- early detection through inspection of genitals, women Pap smear to screen for abnormal cervical cells
- three effective HPV vaccines have been approved by the FDA: Ceravix, Gardasil, and Gardasil 9)

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35
Q

Adenoviruses

A
  • non enveloped, dsDNA
    30 types associated with human disease (oncogenic only in animals)
  • infect lymphoid tissue, respiratory and intestinal epithelia and conjunctiva
  • spread by respiratory and ocular secretions
  • causes colds, pharyngitis, conjunctivitis, keratoconjunctivitis, acute hemorrhagic cystitis
    Severe cases with interferon.
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36
Q

Poxviruses

A

Produce eruptive skin pustules (pocks or pox) that leaves scars
- largest and most complex animal viruses
- have the largest genome of all viruses
- dsDNA
- multiply in cytoplasm in factory areas (break the normal “rules”)
- specificity for cytoplasm of epidermal cells and subcutaneous connective tissues

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37
Q

Smallpox (variola)

A

First (and ONLY) disease to be eliminated by vaccination - maybe Guinea Worm Disease - others are painfully close (polio, measles, mumps, rubella, tape worm, filariasis)
- exposure through inhalation or skin contact
- infection associated with fever, malaise, prostration, and a rash
- Variola major: highly virulent, caused toxemia, shock, and intravascular coagulation
- Variola minor: less virulent

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38
Q

What enabled smallpox to be eradicated

A
  1. Vaccine - effect prophylactically and therapeutically
  2. Human only host
  3. Clear mechanism of transmission - isolation to prevent spread
  4. Obvious signs of disease
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39
Q

Smallpox Vaccination

A
  • the smallpox vaccine uses a single drop of vaccina virus punctured into the skin with a double pronged needle
  • routine vaccination ended in 2002 for military and medical personnel
  • reintroduced to address mpox outbreak in 2022
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40
Q

Monkeypox (mpox)

A

MPOX is typically associated with small animals (guinea pigs, not just simians)
- two common clades associated with human infections (West African/Congo Basin)
- 2022 outbreak associated with the less severe West African clade
- not considered an STI however in 2022 primarily associated MSM

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41
Q

Other Pox Virus Diseases

A

Molluscipoxvirus: much more common Poxviruses. It causes a skin disease called molluscum contagious (think waxy warts)
- distributed throughout the world, with highest incidence occurring in certain Pacific Islands
- in endemic areas, it is primarily an infection of children
- transmittted by direct contact and fomites
- in US, most commonly an STD
- lesions are small, smooth macules in genital area and thighs
- AIDS patients suffer an atypical form which attacks the skin of the face and forms tumor-like growth
Treatment: freezing, electrical cautery, chemical agents (similar to warts)
- many mammalian groups host some poxvirus - cowpox, rabbit pox, mouse pox, elephant pox
- monkeypox in humans - skin pocks, fever, swollen lymph nodes
- cowpox in humans - rare, usually confined to hands; cutaneous sites can be involved

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42
Q

Herpesviruses

A
  • all members show latency and cause recurrent infection; viral DNA forms episome
  • clinical complications of latency and recurrent infections become more severe with advancing age, cancer chemotherapy, or other conditions that compromise the immune defenses
  • common and serious opportunists among AIDS patients
  • large enveloped Icosahedral dsDNA
  • replicates within nucleus
  • most successful virus in humans
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43
Q

Human Herpesvirus Classification

A
  • HHV1 & HHV2: (HSV - herpes simplex virus 1 & 2) - fever, blisters, and genital infections
  • HHV3: (VZV - varicella-zoster virus) - chickenpox and shingles
  • HHV4: ( EBV - Epstein-Barr Virus) - associated with infection of the lymphoid tissue
  • HHV5: (CMV - cytomegalovirus) - infects the salivary glands and other visceral
  • HHV6/7: (HHV) - roselola
  • HHV8: (KSHV) - implicated in kaposi sarcoma
44
Q

Herpes Simplex Virus

A

Human are susceptible to 2 varieties:
- HSV1: usually lesions on the oropharynx, cold sores, fever blisters - occurs early in childhood
- HSV2: lesions on genitalia, possibly oral - occurs in ages 14-29 - can be spread without visible lesions
Transmission by direct exposure to secretions consigning the virus; active lesions most significant source; genital herpes can be changed transmitted in the absence of lesions
- HSV multiplies in sensory neurons, moves to ganglia
- HSV1 enters 5th cranial nerve
- HSV2 enters lumbosacral spinal nerve trunk ganglia
Recurrent infection is triggered by various stimuli - fever, UV radiation, stress, mechanical injury
Newly formed viruses migrate to body surfaces, producing a local skin or membrane lesion

45
Q

Herpes Simple Virus: Type 1

A
  • Herpes labialis: (fever blisters or cold sores) - most common recurrent HSV-1 infection - herpetic gingivostomatitis especially in young children - inflammation of the oral mucosa (gums, tounge, soft palate, and lips)
  • Herpetic Keratitis: (ocular herpes) - inflammation of the eye, latent virus travels into the ophthalmic rather than the mandibular branch of trigeminal nerve - gritty feeling in the eye, conjunctivitis, sharp pain, and sensitivity to light
46
Q

Herpes Simplex Virus: Type 2

A
  • genital herpes: starts with malaise, anorexia, fever, bilateral swelling and tenderness in the groin; clusters of sensitive vesicles on the genitalia, perineum, and buttocks; urethritis, painful urination, cervicitis, itching; vesicles ulcerate
  • recurrent bouts usually less severe, triggered by menstruation, stress, and concurrent bacterial infection
47
Q

Herpes of the Newborn

A

HSV-1 and HSV-2 infections are potentially fatal in the neonate and fetus
- infant contaminated by mother before or during birth; hand transmission by mother to infant
- infection of mouth, skin, eyes, CNS
Preventative screening of pregnant women; delivery by c-section if outbreak at the time of birth

48
Q

Miscellaneous Herpes Infections

A

Herpetic whitlow: HSV-1&2 can penetrate a break in the skin and cause a localized infection, usually on one finger; extremely itchy and painful
- workers in the fields of obstetrics, gynecology, dentistry, and respiratory therapy at greatest risk
HSV-1 encephalitis: rare complication but most common sporadic form of viral encephalitis in the US, life threatening - those with underlying immunodeficiency are prone to severe disseminated herpes

49
Q

Diagnosis, treatment, and control of Herpes Simplex

A
  • Diagnosis: vesicles and exudate are typical diagnostic symptoms, scrapings from base of lesions showing giant cells, culture and specific tests for diagnosing severe or disseminated HSV; direct fluorescent antibody tests
  • Treatment: acyclovir, famiciclovir, valacyclovir; topical medications - one of the few viral diseases we have therapeutic options for
50
Q

Varicella-Zoster Virus (VZV)

A

Humans only natural host. Infection transmitted by respiratory droplets and contact
- primary infection: varicella (chickenpox) - characteristic vesicles - virus enters neurons and remains latent
- reaction of the viruses - Herpes zoster (shingles) - dermatomes. More common in older patients
- activated in ganglion by stress - viruses migrate down sensory nerve to skin
*multiple dermatome or bilateral lesions = immune suppression

51
Q

Diagnosis treatment, and control of VZV infection

A

Diagnosis: cutaneous manifestations of varicella and shingles are sufficiently characteristic for ready clinical recognition
- shingles can be confirmed from multinucleate giant cells in stained smears prepared from vesicle scrapings
- unequivocal shingles identification with florescent antibody detection of viral antigen in skin lesions, dna typing, or culture
Treatment: treat symptoms in uncomplicated infections; acyclovir, famciclovir, interferon for systemic disease - live attenuated vaccine (varivax) for chickenpox and shingles

52
Q

Epstein-Barr Virus (EBV)

A

Think B cells!
Ubiquitous virus: infects lymphoid tissue and salivary glands
Transmission - direct, oral contact and contamination with saliva
- in industrialized countries, college-age population is vulnerable to infectious mononucleosis (mono - kissing disease)
- by mid-life, 90-95% of all people are infected
- anyone with an immune deficiency is highly susceptible
Infectious mononucleosis - sore throat, high fever, cervical lymphadenopathy; develop after 30-50 day incubation
Dormancy in B cells; reactivated may be asymptomatic

53
Q

Complications associated with EBV

A

Burkitt Lymphoma: B cell malignancy
- usually develops in jaw and grossly swells the cheek
- affects Central African children 4-8 years old
- may be associated with chronic coinfections with malaria
Nasopharyngeal carcinoma: malignancy of epithelial cells
- affects older Chinese and African

54
Q

Diagnosis and Treatment of EBV infection

A

Diagnosis
- differential blood count shows lymphocytosis, neutropenia, and large atypical lymphocytes
- serological assays to detect antibodies and antigen
Treatment: directed at relief of symptoms of fever and sore throat
- disseminated disease may be treated with IV gamma, globulin, interferon, acyclovir, and monoclonal antibodies

55
Q

The Cytomegalovirus (CMV) Group

A

Produce giant cells with nuclear and cytoplasmic inclusions
Transmitted in saliva, respiratory mucus, milk, urine, semen, cervical secretions
- commonly latent in various tissues
- most infections are asymptomatic
- 3 groups develop a more virulent form of disease: fetuses, newborns, immunodeficient adults
Newborns may exhibit enlarged liver and spleen, jaundice, capillary bleeding, microcephaly, and ocular inflammation; may be fatal
- babies who survive develop neurological sequelae, hearing, visual disturbances and mental retardation
Perinatal CMV infection - mostly asymptomatic, or pneumonitis, and a mononucleosis-like syndrome
Transplant patients - pneumonitis, hepatitis, myocarditis, meningoencephalitis (David Vetter)
AIDS patients - CMV mononucleosis, disseminated CMV, retinitis

56
Q

Human Herpes Virus 6 & 7

A

Human B-lymphotrophic virus
- transmitted by close contact with saliva and other secretions; very common
- causes rosella, an acute febrile disease in babies 2-12 months; begins with fever, followed by a faint maculopapular rash; usually self-limited
- adults may get mono-like symptoms, lymphadenopathy and hepatitis
- over 70% of MS patients show signs of infection
- clinical studies have shown significant relationship between HHV-6 and Hodgekin’s lymphoma, oral carcinoma, certain T cell leukemias
- HHV-7 is closely related to HHV-6 and causes similar diseases

57
Q

Disease of Herpesvirus 8

A

Kaposi’s sarcoma-associated virus (KSHV) or HHV-8 is linked with common tumor of AIDS patients; also may be involved in multiple myeloma

58
Q

Hepadnaviruses

A
  • enveloped DNA viruses
  • never been grown in tissue culture
  • unusual genome containing both double and single stranded DNA (weird - own Baltimore classification)
  • tropism for liver
59
Q

Hepatitis B

A

Multiplies exclusively in the liver, which continuously seeds blood with viruses - chronic
- 10^7 virions/mL blood
- minute amounts of blood, blood products can transmit infection; sexually transmitted. High incidence among homosexuals and drug addicts
- increases risk of liver cancer - hepatocellular carcinoma
- virus enters through break in skin or mucous membrane or by injection into bloodstream
Reaches liver cells, multiplies and releases viruses into blood; average 7 week incubation - most exhibit few overt symptoms and eventually develop HBV immunity
- some patients experience malaise, fever, chills, anorexia, abdominal discomfort, and diarrhea
- fever, jaundice, rash, and arthritis in more severe cases
- small number of patients develop chronic liver disease - necrosis and cirrhosis
- characteristics: DNA virus, has an envelope, chronic carrier, transmission through blood, semen, and sexual contact, 1-6 month incubation period, fever, rash, arthritis, jaundice,

60
Q

Diagnosis Managemnet, and Prevention of Hep B

A

Diagnosis based on examination of risk factors, serological tests to detect viral antibodies or antigen; radioimmunoassay and ELISA tests for surface antigen
Screening of blood transfusion, semen for sperm banks, organs for transplant, and routine prenatal testing of all pregnant women
Mild cases managed by treatment of symptoms and supportive care; chronic infections treated with interferon
Prevention: passive immunization with HBIG for persons exposed, or possibly exposed, including neonates born to infected mothers
- primary prevention is vaccination for high risk individuals and encouraged for all newborns and infants
- vaccine derived from surface antigen from cloned yeast - 3 doses with boosters
- vaccine derived from purified sterile antigen extracted from carrier blood; mainly for people who have yeast allergies

61
Q

Hep A and E

A

Acute and spreads fecal-orally

62
Q

Hep B, C, and D

A

Spread by blood and fluids
- chronic
- cirrhosis and cancer

63
Q

Reoviruses

A

Non-enveloped segmented dsRNA viruses
- unusual double stranded RNA genome
Two best known:
1. Reovirus: cold-like upper respiratory infection enteritis
2. Rotavirus: oral-fecal transmission; primary viral cause of mortality and morbidity resulting from diarrhea in infants and children
#1 Primary Cause of Diarrhea in infants/children and death from these diarrheal disease (500,00 a year)
In the US, Rotavirus used to be primary cause of infant hospitalizations
- Rotateq and Rotarix - attenuated vaccine

64
Q

Caliciviruses

A

Non-enveloped Nonsegmented ssRNA Viruses
- Norwalk sheet best known; Noroviruses believed to cause 1/3rd of all viral gastroenteritis cases (20 million/yr)
- Currently these are described as Noro-like viruses (NLVs)
- Transmitted by fecal-oral route
- infections in all ages at any time of the year
- acute onset, nausea, vomiting, cramps, diarrhea, chills
- Dr. L’s description, “violent both ender”
- rapid and complete recovery
*Cruise Ship Virus - boats have been quarantined (long before COVID-19) as a consequence of recurrent outbreaks
*Hep E used to be considered a Calci Virus

65
Q

Picornaviruses

A

Non-enveloped nonsegmented ssRNA
- are named for their small (Pico) size and their RNA core Large family of viruses significant to human health (the “herpes” of the RNA chart). Many emerging threats D68 are picornaviruses
Important genera
- Enterovirus: poliovirus, HAV
- Rhinovirus
- Cardiovirus: infects heart and brain

66
Q

Picornaviruses

A

Enteroviruses: general features
- Entero: fecal-oral transmission, indirect fomite transmission - poor quality increases risk - general unhygienic living increase risk

67
Q

Poliovirus and Poliomyelitis

A

Poliomyelitis (polio): acute enteroviral infection of the spinal cord that can cause neuromuscular paralysis
Poliovirus: naked capsid; resistant to acid, bile, and detergents; can survive stomach acids when ingested
*worldwide vaccination programs have reduced the number of cases; eradication is expected

68
Q

Polio - Spectrum of Outcomes

A

Transmitted by fecal-oral route
- polioviruses adhere to receptors of mucosal cells in oropharynx and intestine, multiply in number and shed in throat and feces
- some virions leak into blood
- most infections are short term, mild viremia
- some develop mild nonspecific symptoms of fever, nausea, sore throat, myalagia
- if viremia persists, virus spreads to spinal cord and brain
- if nervous tissue is infected but not destroyed - muscle pain and spasm, meninges inflammation, and vague hypersensitivity
- invasion of motor neurons causes flaccid paralysis
- decades later post-polio syndrome (PPS) - progressive muscle deterioration; occurs in 25%-50% of patients infected with poliovirus in childhood
- 90% asymptomatic

69
Q

Paralytic disease

A

Paralysis of the muscles of the legs, abdomen, and back, intercostals, diaphragm, pectoral girdle, and bladder can result
Bulbar poliomyelitis - rare cases, requires mechanical respirators
- brain stem, medulla, or cranial nerves affected
Severe deformities of the trunk and limbs develop follows muscle atrophy
- spine, shoulder, hips, knees, feet

70
Q

Treatment and Prevention of Polio

A

Treatment is largely supportive for pain and suffering; respiratory failure may require artificial ventilation; physical therapy may be needed
Prevention is vaccination
- inactivated polio vaccine - Salk Vaccine
- oral polio vaccine, Sabin vaccine, attenuated virus, - no longer recommended in the US
- worldwide eradication is being attempted

71
Q

Nonpolio Enterviruses

A

Coxsackieviruses: hand-foot-mouth disease

72
Q

Hepatitis A Virus and Infectious Hepatitis

A

Cubical Picornaviruses relatively resistant to heat and acid
Not carried chronically (acute infections), principal reservoirs are asymptomatic, short-term carriers or people with clinical disease
- fecal-oral transmission; multiplies in small intestine and enters the blood and is carried to the liver
- most infectious subclinical or vague, flu-like symptoms occur; jaundice is seldom present
Treatment: no specific treatment once the symptoms begin
Prevention
- vaccination
- inactivated of attenuated viral vaccines
- pooled immune serum globulin for those entering into endemic areas or post known exposure
- clean water and hygiene

73
Q

Human Rhinovirus (HRV) - Colds #1

A
  • more than 110 serotypes associated with the common cold
  • unique molecular surface markers makes development of a vaccine unlikely
  • many strains circulating in the population at one time; acquired from contaminated hands and fomites
  • sensitive to acidic environments; optimum temperature is 33 degrees Celsius
  • symptoms: headache, chills, fatigue, sore throat, cough, nasal drainage
  • treatment: treat the symptoms
  • handwashing and care in handling nasal secretions
74
Q

Arboviruses

A

Viruses spread by arthropod vectors
- arthropod vectors: mosquitoes, ticks, flies, and gnats
- 400 viruses
- toga viruses, flaviviruses, some bunyaviruses, and reoviruses
- most illnesses caused by these viruses are mild fever; some may cause severe encephalitis, and life-threatening hemorrhagic fever

75
Q

Hemorrhagic Fever

A

Dengue fever: flavivirus carried by Aedes mosquitoes; not in US - usually mild infection
- dengue hemorrhagic shock syndrome (breakbone fever) - extreme muscle and joint pain; can be fatal

76
Q

The influence of the Vector

A
  • vectors and viruses tend to be clustered in the tropics and subtropics; many temperate zones have periodic epidemics
  • arbovirus life cycles are closely tied to the ecology of the vectors
  • infections show a peak incidence when the arthropod is actively feeding and reproducing
  • humans can serve as dead-end, accidental hosts or they can be a maintenance vector
    *controlling the vector controls the disease
77
Q

Togavirus - The EE’s and Chiky

A

Arboviruses
- the wrapping (envelope) needs protection in the vector as it moves around new hosts. Human are accidental, dead-end hosts for these viruses w
Chikungunya: native transmission in the US started in 2014
- fever and joint pain

78
Q

Togavirus - Rubella

A

German measles
- endemic disease
- most cases reported are adolescents and young adults
- transmitted through contact with respiratory secretions
- diagnosis based on serological testing
- no specific treatment available
- attenuated viral vaccines MMR - the R in the MMR
Two clinical forms
1. Postnatal rubella: malaise, fever, sore throat, lymphadenopathy, rash, generally mild, lasting about 3 days
2. Congenital rubella: infection during 1st trimester most likely to induce miscarriage or multiple defects such as cardiac abnormalities, ocular lesions, deafness, mental and physical retardation

79
Q

Flavivirus - the Arbovirus

A

West Nile Virus Encephalitis: transferred to humans by mosquitoes infected by birds blood - 80% of people infected show no symptoms; less than 1% develop neurological illness (encephalitis or meningitis)
Zika Virus: symptoms very similar to infection with chikungunya or dengue viruses. Birth defects of mother infected during pregnancy
Dengue fever: flavivirus carried by Aedes mosquitoes; usually mild infection
- it’s the second time that gets you (strain matters) - dengue hemorrhagic shock syndrome (breakbone fever) - extreme muscle and joint pain; can be fatal

80
Q

Flavivirus - Hep C

A

Acquired through blood contact - blood transfusions, needle sharing by drug absusers
- more common to have chronic liver disease, without overt symptoms
- cancer may also result from chronic HCV infection
Treatment
- depends on viral genotype
- genotype 1 - sofosbuvir and ledipasvir for 12 weeks
- other genotypes are usually treated for 12 weeks with sofosbuvir, coupled with velpatasvir
Previously - with interferon and ribavirin to lessen liver damage; no cure and no vaccine

81
Q

Coronaviruses

A
  • Relatively large RNA viruses with distinctively spaced spikes on their envelopes
  • common in domesticated animals
  • 5 types of human coronaviruses have been characterized, among these are agents of…
    Common Cold
  • some forms of viral pneumonia and myocarditis
  • some human enteric infections
  • severe acute respiratory syndrome (SARS): airborne transmission - 9% of cases fatal
  • middle eastern respiratory syndrome - 40% of cases fatal
82
Q

SARS associated with Coronavirus

A

SARS and MERS
- transmitted through droplet or direct contact
- fever, body aches, malaise
- may or may not experience respiratory symptoms with breathing problems; severe cases can result in respiratory distress and death
- treatment is supportive

83
Q

Covid 19 Time Course

A

Two phases
1. Host responds to virus
2. Host responds to own inflammatory response
- not everyone with virus reaches this stage

84
Q

Retroviruses

A
  • convert ssRNA into dsDNA using reverse transcriptase
  • dsDNA integrates into host cell genome and serves as a template for mRNA synthesis and genome synthesis
85
Q

HIV Infections and AIDS

A

Human immunodeficiency virus (HIV)
- acquired immunodeficiency syndrome
- first emerged in early 1980s
- severe pneumonia caused by Pneumocystis jirovecii (ordinarily a harmless fungus)
- a rare vascular cancer called Kaposi Sarcoma
- sudden weight loss, swollen lymph nodes
- general loss of immune function
- 1959 first documented case of AIDS

86
Q

Characteristics of Human Retrovirus

A

HIV-1 and HIV-2
- T-cell lymphotropic viruses 1 and II - leukemia and lymphoma
- HIV can infect host cells that have the required CD4 marker + a co-receptor

87
Q

Epidemiology of HIV infection

A

Transmission occurs by direct and specific routes
- mainly through sexual intercourse and transfer of blood or blood products
- babies can be infected before or during birth, and from breast feeding
- HIV does not survive long outside the body
- first nationally notifiable in 1984
- 6th most common cause of death among people aged 25-44 years in the US
- men account for 75% of new infections
- IV drug abusers can be HIV carriers; significant factor in spread to heterosexual population
- in 2009, the number of infected individuals worldwide is estimated to be 35 million with 1.2 million in the US

88
Q

Stages of HIV Infection and AIDS

A

Pathology tied to two factors
1. The level of viruses
2. The level of T cells in the blood
primary effects of HIV infection
- extreme leukopenia -lymphocytes in particular formation of giant T cells and other syncytia virus spreads
- infected macrophages release the virus in CNS, with toxic effect, inflammation
Secondary effects of HIV
- CD4 lymphocytes destruction - opportunistic infections and malignancies during full-blown AIDS

89
Q

Diagnosis of HIV infection

A

Testing based on detection of antibodies specific to the virus in serum or other fluids; done at 2 levels
Initial screening
- ELISA, latex agglutination, and rapid antibody tests
- Rapid results but may result in false positives
Follow up with western blot analysis to rule out false positives
False negatives can occur; persons who may have been exposed should be tested a second time 3-6 months later

90
Q

Preventing and treating HIV infection

A

No vaccine
- monogamous sexual relationships
- condoms
- universal precautions
No cure; therapies slow down the progress of the disease or diminish the symptoms
- inhibit viral enzymes: RT, protease, integrase
- inhibit fusion
- inhibit viral integration
- highly active anti-retro viral therapy (most effective) HAART therapy

91
Q

Bunyaviruses and Arenaviruses

A

Transmitted zoonotically; cause periodic epidemics; extremely dangerous; bio safety level 4
Bunyaviruses - typically transmitted by insects and ticks
- California encephalitis, rift valley fever, Korean hemorrhagic fever
- American bunyavirus is a hantavirus, Sin Nombre
- hantavirus pulmonary syndrome (HPS) emerging disease; high fever, lung, edema, and pulmonary failure; 33% mortality rate
- carried by deer and harvest mice; transmitted via airborne dried animal waste
Arenavirus
- Lassa fever, Argentine hemorrhagic fever, blovian hemorrhagic fever, and lymphocytic chorionmeningitis
- closely associated with rodent host
- transmission through aerosols and contact

92
Q

Rabies

A

Rhabdovirus family; genus lyssavirus
Enveloped, bullet-shaped virions
Slow, progressive zoonotic disease
Primary reservoirs are wild mammals; it can be spread by both wild and domestic mammals by bites, scratches, and inhalation of droplets
Virus enters through bite, grows at trauma site for a week and multiplies, then enters nerve endings and slowly advances toward the ganglia, spinal cord and brain
Infection cycle completed when virus replicates in the salivary glands
Clinical phase of rabies:
- prodromal phase - fever, nausea, vomiting, headache, fatigue; some experience pain, burning, tingling sensations at site of wound
- furious phase - agitation, disorientation, seizures, twitching, hydrophobia
- dumb phase - paralyzed, disoriented, stuporous
- progress to comma phase, resulting in death

93
Q

Diagnosis and management of rabies

A

Often diagnosed at autopsy - intracellular inclusions (Negri bodies) in nervous tissue
Bite from wild or stray animals demands assessment of the animal, meticulous wound care, and specific treatment
Preventive therapy initiated if signs of rabies appears
Treatment - passive and active post exposure immunization
- infuse the wound with human rabies immune globulin (HRIG) and globulin; vaccination with human diploid cell vaccine (HDCV), an inactivated vaccine given in 6 doses with 2 boosters
Control - vaccination of domestic animals, elimination of strays, and strict quarantine practices
- live oral vaccine incorporated into bait for wild animals

94
Q

Filovirus

A

Ebola - BSL4, hemorrhagic fever
- describes the severe, multi system syndrome seen in Ebola epidemics
- host vascular system is damaged, so vascular leakage of fluids is accompanied by diminished clotting ability

95
Q

Paramyxoviruses

A

F-protein: fascilitastes fusion of virus with cell, but will also result in cells fusing together. Forms syncytium or giant multi-nucleated cells
- Four important paramyxoviruses
- parainfluenza - Croup
- mumps
- measals
- RSV - respiratory syncytial virus

96
Q

Parainfluenza

A

Widespread as influenza but more benign
Respiratory transmission
Seen mostly in children
- primary infection in infants can be severe to be life-threatening
Characteristic “seal-bark” cough, “croup” cough
Minor cold, bronchitis, bronchopneumonia, coup
No specific treatment available; supportive therapy; cool, dry air

97
Q

Mumps: epidemic parotits

A

Epidemics parotitis: self-limited illness, associated with painful swelling of parotid salivary glands
- humans are the only reservoir
- 40% of infections are subclinical; long-term immunity
- 300 cases in US/year
- incubation 2-3 weeks fever, muscle pain, and malaise, classic swelling of one or both cheeks
- usually uncomplicated invasion of other organs; in 20-30% of infected adult males, epididymis and testes become infected; sterility is rare
- symptomatic treatment
- live attenuated vaccine MMR

98
Q

Measles

A

Also known as red measles and rubeola
- different from German measles
- very contagious; transmitted by respiratory aerosols
- humans are the only reservoir
- less than 100 cases/yr in US, frequent cause of death worldwide
Virus invades the mucosal lining of respiratory tract
Initial symptoms
- sore throat, dry cough, headache, conjunctivitis, lymphadenitis, fever
Koplik’s spots: oral lesions
Exanthem: characteristic red maculopapula eruption on the head, progressing to trunk and extremities to cover most of the body

99
Q

Measles

A

Most serious complication is subacute sclerosing panendephalitis (SSPE), a progressive neurological degeneration of the cerebral cortex, white matter, and brain stem
- 1 case in a million infections
- involves a defective virus spreading through the brain by cell fusion and destroys cells
- leads to coma and death in months or years
Attenuated viral vaccine: MMR

100
Q

Respiratory Syncytial Virus (RSV)

A

Infects upper respiratory tract and produces giant multinucleate cells
Most prevalent cause of respiratory infection in children 6 months or younger; most susceptible to serious disease
- epithelia of nose and eye portal of entry; replicates in nasopharynx
- fever, rhinitis, pharyngitis, otitis, croup
Treatment:
- synagis, a monoclonal antibody that blocks attachment to cells, RSV immunoglobulin - prophylaxis for exposed children
- ribavirin, inhaled antiviral drug

101
Q

Biology of Orthomyxoviruses - Influenza

A

3 distinct influenza virus types: A, B, C
*Type A causes most infections
Influenza nomenclature chronicles virus type, animal of origin, location, and year of origin
1. Influenza A: after 2003, strains of this virus that usually infects birds underwent an antigenic shift and began to infect humans
2. Influenza B: only undergo antigenic drift, no antigenic shift
3. Influenza C: known to cause only minor respiratory disease; probably not involved in epidemics

102
Q

Influenza A

A
  • acute, highly contagious respiratory illness
  • seasonal, pandemics; among top 10 causes of death in Us - most commonly among elderly and small children
  • binds to ciliated cells of respiratory mucosa
  • causes rapid shedding of cells, stripping the respiratory epithelium; severe inflammation
  • fever, headache, myalgia, pharyngeal pain, shortness of breath, coughing
  • weakened host defenses predispose patients to secondary bacterial infections, especially pneumonia
103
Q

Influenza infection

A

Virus attaches to, and multiplies in cells if respiratory tract, segments of RNA genome enter the nucleus, finished viruses are assembled and bud off the cell

104
Q

Influenza Glycoproteins

A

Key to influenza are glycoproteins spikes
- Hemagglutination (H): 15 subtypes; most important virulence factor; binds to host cell
- Neuraminidase (N): 9 subtypes - hydrolyzes mucus and assists viral budding and release
Both glycoproteins frequently undergo genetic changes, decreasing (not eliminating) the effectiveness of the host immune response

105
Q

Influenza Mutation

A

Constant mutation is called antigenic drift - gradually change their amino acid composition
Antigenic shift: one of the genes or RNA strands is substituted with a gene or strand from another influenza virus from a different animal host
- genome of virus consists of 10 genes encoded on 8 separate RNA strands
- requires co-infection with two strains of virus

106
Q

Diagnosis, treatment, prevention of influenza

A

Diagnosis:
- rapid immunofluorescence tests to detect antigens in a pharyngeal specimen
- serological testing to screen for antibody titer
Treatment:
- control symptoms; amantadine, rimantadine, zanamivir (relenza), and oseltamivir (tamiflu)
- flu virus has developed high rate of resistance to amantadine and rimatadine
Annual vaccine recommended