Microbiology review week 7

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Microbiology review week 7

• efking_at_u.washington.edu

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What well cover today

• Viruses
• More viruses
• Did I mention viruses?

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Lets start with DNA viruses

• ds ss
• Enveloped naked
  naked
• Resp saliva parenteral resp
  direct B19
• Pox herpes Hep B adeno
  papilloma
• polyoma

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Lets start with DNA viruses

• ds ss
• Enveloped naked
  naked
• Resp saliva parenteral resp
  direct B19
• Pox herpes Hep B adeno
  papilloma
• polyoma

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Lets start with DNA viruses

• ds ss
• Enveloped naked
  naked
• Resp saliva parenteral resp
  direct B19
• Pox herpes Hep B adeno
  papilloma
• polyoma

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Poxviridae

• Linear dsDNA in dumbbell shape surrounded by 2
  envelopes
• brick shaped virion (pox in a box)
• Differs from most DNA viruses - replicates in
  cytoplasm
• Thus carries all enzymes needed for RNA synthesis
• Produces cell lysis to release virions
• Evades immunity by cell-cell spread
• Variola
• Monkeypox
• Molluscum contagiosum

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Variola(not to be confused with Varicella or
vermicelli)

• Smallpox
• Humans only reservoir all infections produce
  overt disease
• Spread via inhalation, close contact
• Replicates in cells in upper respiratory tract
• Disseminates via lymphatics
• Secondary viremia
• Seeds liver, spleen, BM, dermis
• Characteristic pustular rash
• Dx clinical, cell culture
• Vaccine vaccinia (cowpox avirulent, mostly)
• Occasional dissemination
• rare mortality in immunosuppressed

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Monkeypox

• Disease looks a lot like smallpox
• Get from direct contact with animals
• Cow, sheep, goat, monkey reservoir
• Mainly in Africa

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Molluscum contagiosum

• Nodular to wartlike lesions
• Spread by direct contact or fomites
• More common in kids, AIDS pts
• Humans only reservoir
• Benign proliferation of epithelium on trunk,
  genitals, proximal extremities

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Lets start with DNA viruses

• ds ss
• Enveloped naked
  naked
• Resp saliva parenteral resp
  direct B19
• Pox herpes Hep B adeno
  papilloma
• polyoma

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Herpes viruses

• Transmitted by saliva other stuff - sex, etc.
• All herpes viruses can develop a latent state
  lytic and latent cycles
• Cell-mediated immune response
• ? subgroup cytopathic, lytic infections
• Multinucleate, giant syncitial cells with
  intranuclear inclusions
• Cause vesicles (blisters)
• HSV-1, HSV-2, VZV
• ? group less cytopathic
• HHV-6, CMV
• ? group less cytopathic
• EBV, HHV-8
• Can treat most of these with antivirals
  (acyclovir, gancyclovir)

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HSV-1

• Primary infection
• Asymptomatic in 99
• Gingivostomatosis - swollen gums, vesicles, fever
• Reactivation - about 1/4 of infected
• Often reactivates from trigeminal ganglia
• Cold sores, fever blisters
• Herpatic keratitis - corneal blindness
• Encephalitis
• Disseminated infection in immunocompromised
• Can cause genital neonatal herpes, but HSV-2
  more commonly does
• Latency in neurons
• Dx demonstrate viral Ag or DNA, serology

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HSV-2

• Primary infection
• Often subclinical, can be fever, myalgia
• Reactivation
• Genital herpes
• Painful vesicles on genitals burning, itching,
  dysuria
• Neonatal herpes -
• can cross blood-placenta barrier - congenital
  defects
• Or acquire during delivery
• Meningitis
• Disseminated disease in immunocompromised
• Can cause eye/skin/oral disease, but usually
  HSV-1
• Latency in neurons
• Dx cytopathology, demonstrate viral Ag/DNA

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VZV

• Primary disease
• Chicken pox
• rash starting on face trunk - dewdrops on a
  rose
• In adults immunocompromised, can have serious
  disease
• Reactivation
• Shingles
• Reactivates from latency in dorsal root ganglia
• Burning, painful vesicles, restricted to
  dermatome
• Increasing incidence with age
• Dx cytology, Ag/DNA detection
• Live attenuated vaccine

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HHV-6

• Roseola
• High fever followed by rash
• Febrile seizures
• Latency in B cells
• Common in infants

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CMV

• Primary infection
• Most are asymptomatic
• Mononucleosis
• Heterophile negative
• Congenital disease
• Microcephaly, rash, retardation, deafness
• Reactivation disease in immunocompromised
• Disseminated infection
• In BMT pneumonia
• In HIV retinitis
• Latency in monocytes, T-cells, BM stroma
• Dx cytology - nuclear AND cytoplasmic
  inclusions

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EBV

• Mononucleosis
• Heterophile positive
• Lymphocytosis, hepatosplenomegaly, pharyngitis
• Encephalitis
• Lymphoprolifertative disease
• Infects transforms B cells
• Burkitts lymphoma
• Nasopharyngeal cancer
• Hairy leukoplakia in AIDS pts
• Disease post transplants
• Dx Downey cells, heterophile Abs
• Rx only leukoplakia (acyclovir)

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HHV-8

• Kaposis sarcoma
• Especially in males, immunosuppressed
• NOT ubiquitous
• Infects B cells, spindle cells

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Lets start with DNA viruses

• ds ss
• Enveloped naked
  naked
• Resp saliva parenteral resp
  direct B19
• Pox herpes Hep B adeno
  papilloma
• polyoma

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adenoviruses

• Direct/oral contact, fomites
• Many serotypes
• Upper respiratory illnesses
• Rhinitis
• Pharyngitis conjunctivitis
• Pertussis-like illness
• Gastroenteritis
• Keratoconjunctivitis
• Hemorrhagic cystitis nephritis
• Pneumo, hepatitis in immunocompromised
• Lytic, latent and oncogenic infections
• Dx smudge cells
• Oral live vaccine in military

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Polyomavirus

• Ubiquitious, worldwide
• Respiratory transmission
• BK virus
• Mild/asymptomatic infection in kids
• Hemorrhagic nephritis in immunosuppressed
• Latently infects kidney cells
• JC virus
• Progressive multifocal leukoencephalopathy in
  immunosuppressed
• Demyelination in CNS - impaired speech,
  paralysis, death
• Latent in B cells, replicates in oligodendroglia
  in reactivation infection

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Lets start with DNA viruses

• ds ss
• Enveloped naked
  naked
• Resp saliva parenteral resp
  direct B19
• Pox herpes Hep B adeno
  papilloma
• polyoma

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HPV

• Spread by direct contact, sex, fomites
• Lots of serotypes with tropism for various
  anatomic regions
• Cutaneous warts
• Genital warts
• Perinatal transmission - laryngeal papillomas
• Cervical cancer (HPV16, 18)
• Integration of DNA in cervical epithelial cells
• Pathogenesis lytic, persistant latent
  infections
• E6 - binds p53
• E7 - binds Rb
• Dx koliocytes on pap smear, PCR
• Tx surgical removal

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Lets start with DNA viruses

• ds ss
• Enveloped naked
  naked
• Resp saliva parenteral resp
  direct B19
• Pox herpes Hep B adeno
  papilloma
• polyoma

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B19

• Fifths disease
• Slapped cheeks, lacy rash on arms, fever
• Rash caused by immune complex deposition
• Congenital infection - hydrops fetalis
• Aplasic crisis in chronic hemolytic anemia pts
• Persistant anemia in immunocompromised
• Replicates in BM cells - RBC, platelet lineage
• Causes lytic infection
• Dx serology, PCR, cord blood IgM
• Rx immunoglobulin

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A 19 yo male comes to clinic because he had a
single, large, painless ulceration on his penis.
A rapid serological assay was performed which
involved the suspensiion of antigen derived from
beef heart in serum this was positive, and
followed up with another test utilizing antigen
derived from the suspected antigen. This was
also positive. This patient is most likely
infected with

• HSV-1
• H. ducreyi
• T. pallidum
• C. trachomatis (LGV strain)
• HPV

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A 19 yo male comes to clinic because he had a
single, large, painless ulceration on his penis.
A rapid serological assay was performed which
involved the suspensiion of antigen derived from
beef heart in serum this was positive, and
followed up with another test utilizing antigen
derived from the suspected antigen. This was
also positive. This patient is most likely
infected with

• HSV-1
• H. ducreyi
• T. pallidum
• C. trachomatis (LGV strain)
• HPV

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Reinfection or reactivation with this organism is
common in HIV-infected persons, even with CD4
counts 300

• Staph aureus
• HTLV-2
• VZV
• HHV-8

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Reinfection or reactivation with this organism is
common in HIV-infected persons, even with CD4
counts 300

• Staph aureus
• HTLV-2
• VZV
• HHV-8

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On to RNA virusesit gets a lot worse from here
on in. -Hoggle in the Labyrinth
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rotavirus

• Fecal/oral, fomites, nosocomial
• Most common in winter
• 1 cause of infectious diarrhea
• Segmented genome - gene reassortment
• Gastroenteritis
• Vomiting, diarrhea - dehydration
• Kids adults
• Causes lytic infection - destroys vili
• Dx Ag in stool, ELISA
• Rx supportive, oral rehydration
• Vaccine recalled due to intussusception

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Flaviviruses

• One group of the arboviruses (arthropod
  transmitted) - cause encephalitis, fever
• Yellow fever
• Mosquito transmission
• Severe systemic disease - hepatitis,
  coagulopathy, hepatic necrosis
• Dx councilman bodies
• Live virus vaccine
• Dengue virus
• mosquito transmission
• Hemorrhagic fever or breakbone fever
• Rash, fever, back and bone pain
• A small develop hemorrhagic shock upon
  rechallenge with another strain

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Flaviviruses

• Encephalitis meningitis
• Mosquito transmission, bird reservoir humans are
  incidental hosts
• St. Louis - US, summer
• Japanese B - inactivated vaccine available
• West Nile - East coast, esp elderly pts
• Tick transmission
• Powassan - Canada
• Russian
• All enter cell via endocytosis, envelope fuses
  with endosome on acidification replicates in
  cytoplasm
• Rx supportive

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Coronaviruses

• SARS
• (thats all Im going to say about this you know
  more about it than I do)
• Common cold, mainly in kids
• Second most common cause
• Winter spring
• Rare pneumonia
• Transmitted by aerosols, droplets
• Dx not usually done ELISA
• Rx supportive

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Togaviruses

• One group of the arboviruses (arthropod
  transmitted)
• Along with bunyaviruses, flaviviruses
• Two subgroups
• Rubella - exception as NOT transmitted by bug
• Alphaviruses
• WEE, EEE, VEE

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Rubella

• Transmitted by respiratory droplet
• German measles
• Mild febrile illness with rash, lymphadenopathy
• If mom is infected when fetus is
• Cataracts
• Heart disease
• Deafness
• Retardation
• No cell lysis kid excretes virus for years
• Live viral vaccine

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Alphaviruses

• Transmitted by mosquitoes
• Enters cells by endocytosis, fuses with endosome
  on acidification, replicates in cytoplasm,
  released by cell lysis
• Bird reservoir human is incidental host
• Flu-like syndrome and encephalitis
• WEE - W. US, Canada
• VEE - S/Central America, S. US
• EEE - E. US severe encephalitis
• Occasional paralysis, seizures, death
• Dx serology
• No Rx
• Killed vaccine

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Poliovirus

• Fecal/oral, fomites primarily
• Peaks in summer, early fall
• Polio
• Mild illness - most common asymptomatic or
  febrile
• Meningitis
• Paralytic poliomyelitis
• Anterior horn cells destroyed
• Increase risk with age
• Lytic infection
• Dx PCR, cell culture, Ab assay
• Vaccines
• Salk - inactivated
• Sabin - live oral

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Cocksackie

• Fecal/oral
• A hand, foot and mouth disease
• B
• Myocarditis/pericarditis
• Meningitis/encephalitis
• Neonatal sepsis
• Pleurodynia - sudden fever, unilateral pleurisy
• Juvenille diabetes?
• Infects GALT- viremia - infects organs
• Lytic infection
• Dx PCR of CSF, direct isolation
• Rx immunoglobulin as last ditch

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Echoviruses

• Fecal/oral
• Diseases a lot like cocksackie
• Meningitis
• Rash/fever
• Neonatal sepsis
• Mycoarditis
• Lytic infection
• Dx PCR
• Rx plecornaril for meningitis

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Rhinovirus

• Aerosols, fomites, hands
• Fall and spring
• Common cold
• Rhinorrhea, sneezing, sore throat, HA
• Grows best at 33 degrees
• Replicates in cytoplasm, lyses cells
• Dx clinical, cell culture
• Rx none

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Norwalk

• Fecal/oral, shellfish, contaminated food
• Year-round
• Gastroenteritis
• Adults kids
• Diarrhea with vomiting fever (like rotavirus)
• Replicates in cytoplasm, lyses cells
• Dx ELISA, cant culture

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Astrovirus

• Fecal/oral via contaminated foods
• Gastroenteritis
• Kids adults
• Diarrhea without vomiting
• Replicates in cytoplasm, lyses cells
• Dx ELISA, cell culture
• Rx none

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influenza

• Orthomyxovirus types A B
• Segmented genome
• Hemagglutinin - mediates attachment, fusion
• Neuraminidase - mediates virion release
• M2 - proton channel, promotes uncoating and
  release
• Transmitted by respiratory droplet in winter
• Causes the flu - fever, cough
• Complications
• Bacterial/viral pneumonia
• Reyes syndrome
• Post infectious encephalitis
• Endocytosis, fusion with endosome on
  acidification, transcription of genome in
  nucleus, release by lysis
• Dx serology, hemagglutination
• Rx zanamivir (NA), amantadine (M2, type A only)
• Killed vaccine

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Sin Nombre virus

• Hantavirus pulmonary syndrome
• High fever, cough, vomiting, pulmonary edema, CV
  collapse
• Endocytosis, fuses with endosome on
  acidification, replicates in cytoplasm
• Dx RT-PCR, IgM
• Rx ribavirin
• Found in Western US

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Measles virus

• Transmitted by respiratory droplet
• Winter spring
• Rubeola
• High fever, photophobia, cough, Kopliks spots
• Complications
• Pneumonia, hepatitis
• Encephalitis
• Acute
• Post-infectious
• Subacute sclerosing - 5-9 years later
• Persists without lysis in neurons
• Dx clinical, cytoplasmic inclusions and giant
  cells
• Rx Ig post exposure
• Live attenuated vaccine

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Mumps virus

• Mumps
• Parotitis
• Epididymitis/orchitis
• Meningitis, encephalitis
• Pancreatitis
• Carries own RNA-dependent RNA polymerase
• Rx none
• Live vaccine

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RSV

• Very contagious by resp droplet, hands, fomites
• Winter outbreaks
• Disease
• Kids febrile rhinitis pharyngitis
• Adults URI, rhinorrhea - common cold
• Pathogenesis
• F protein - fusion
• G protein - attachment
• Replicates in cytoplasm
• Dx fluorescent Ab, Ag detection
• Rx nebulized ribavirin in premies/immunocompromis
  ed. Maternal Ig not protective

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Parainfluenza

• Respiratory droplet
• 1,2 - autumn 3 - year around
• Disease
• Croup (laryngotrachobronchitis) - infants
• Subglottal edema, tachypnea, tachycardia
• Cold-like Sx - pharyngitis, bronchiolitis,
  pneumonia
• Path
• F - fusion protein
• HN - attachment
• Replicates in cytoplasm
• Dx syncytia, immunofluorescence
• Rx humidity, steroids, epi

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Rabies virus

• Bullet shaped
• Transmitted by inhalation of aerosol, bite of
  infected animal bat reservoir in NW, cats dogs
• World-wide, year around
• Rabies
• Incubation weeks - months
• Prodrome 2-10 days - fever, HA, lethargy, pain
  at bite site - virus is in CNS
• Neurologic phase hydrophobia, encephalitis,
  paralysis, death
• Endocytosis, fuses w/endosome on acidification,
  replicates in cytoplasm, released by budding
• Carried to dorsal root - CNS - salivary glands
• Dx Negri bodies - cytoplasmic inclusions
• Rx vaccine, human If for post-exposre
• Inactivated vaccine

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Filoviruses

• Ebola marburg
• Fulminant hemorrhagic fever
• Flu-like Sx then n/v, diarrhea, rash
• Bleed from everywhere
• Death in up to 90, ebolamarburg
• Fast replication in cytoplasm, cell lysis
• Causes vascular injury, necrosis
• Dx Level 4 containment, RT-PCR, ELISA
• Rx quarantine, Ig, IFN
• Endemic in Africa

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arenaviruses

• Transmited from rodents - people by eating
  contaminated food, fomites, aerosols
• LCM
• Lymphocytic choriomeningitis
• Febrile illness, meningitis
• Dx level 3 containment, serology
• No person-person spread
• Lassa fever
• Fever, coagulopathy, petechiae, hepatic/splenic
  necrosis no vasculitis or CNS lesions
• Dx Level 4 containment, urine serology
• Person - person by bodily fluid contact,
  nosocomial
• Infects macrophages, replicates in cytoplasm,
  released by budding
• Rx supportive

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One last thing

• Prions
• Kuru, CJD, others in humans - genetic,
  spontaneous, food-borne (variant CJD)
• Scrapie, BSE, etc in animals
• Normal protein (PrPc)
• Abnormal protein (PrPsc) - insoluble - amyloid
  can induce misfolding of normal one
• Spongiform encephalooathy
• Incubates up to 30 years
• Dementia, ataxia, aphasia, clonus, death
• Dx brain Bx
• Rx noneavoid mad cow burgers

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Some lists

• viruses transmitted by mosquito
• WEE, EEE, VEE
• Dengue
• Yellow fever
• Flaviviruses - St. Louis, Japanese B, W. Nile
• Stuff you cant culture
• Clostriduim tentani
• M. leprae (except in mouse foot pads)
• Coxiella
• Treponema pallidum
• Pneumocystis carinii
• Norwalk virus

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Virus calendar

• Winter spring summer fall
• Rota Rhino St. Louis Rhino
• Measles polio
• Corona
• RSV
• Influenza para 12
• Para 3
• Norwalk
• rabies

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Which virus must incorporate an RNA-dependent RNA
polymerase in the virion?

• Polio
• Measles
• Retrovirus
• Parvovirus
• Herpesvirus

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Which virus must incorporate an RNA-dependent RNA
polymerase in the virion?

• Polio
• Measles (- strand RNA virus)
• Retrovirus
• Parvovirus
• Herpesvirus

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May cause severe pneumonitis and hepatitis in a
patient with AIDS

• Tuberculosis
• HTLV-2
• Varicella zoster
• HHV-8

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May cause severe pneumonitis and hepatitis in a
patient with AIDS

• Tuberculosis
• HTLV-2
• Varicella zoster
• HHV-8

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Escape from neutralization because of antigenic
change in the envelope proteins is commonly seen
in both hepatitis C and HIV-1 infection

• True
• False

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Escape from neutralization because of antigenic
change in the envelope proteins is commonly seen
in both hepatitis C and HIV-1 infection

• True
• False

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Fungal jeopardy
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Fungal jeopardy
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• All dermatophytes can digest this human protein

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• All dermatophytes can digest this human protein
• Keratin

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Fungal jeopardy
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• These three drugs are good for treating most
  dermatophyte infections

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• These three drugs are good for treating most
  dermatophyte infections
• Tolnaftate
• Griseofulvan
• Terbinafine

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Fungal jeopardy
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• This disease is caused by Malassezia furfur

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• This disease is caused by Malassezia furfur
• Tenia versicolor

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Fungal jeopardy
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• Rose gardeners disease is caused by this organism

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• Rose gardeners disease is caused by this
  organism
• sporothrix schenckii

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Fungal jeopardy
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• This tropical fungus causes verrucous lesions,
  typically after a puncture wound on the foot

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• This tropical fungus causes verrucous lesions,
  typically after a puncture wound on the foot
• chromoblastomycosis

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Fungal jeopardy
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• This disease can be caused by Nocardia and
  Pseudoallescheria boydii in the tropics

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• This disease can be caused by Nocardia and
  Pseudoallescheria boydii in the tropics
• mycetoma

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Fungal jeopardy
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• Fungi that causes sytemic diseases have these
  three things in common

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• Fungi that causes sytemic diseases have these
  three things in common
• Dimorphic
• Saprophytes
• Acquired by inhalation

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Fungal jeopardy
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• This fungus causes disease in the Mississippi and
  Ohio river valleys

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• This fungus causes disease in the Mississippi and
  Ohio river valleys
• Histoplasma

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Fungal jeopardy
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• Diagnosed by finding Mariners wheels in culture

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• Diagnosed by finding Mariners wheels in culture
• Paracoccidiodes

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Fungal jeopardy
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• This fungus causes aflatoxin intoxication as well
  as other diseases

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• This fungus causes aflatoxin intoxication as well
  as other diseases
• aspergillus

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Fungal jeopardy
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• Rhinocerebral, pulmonary, and cutaneous diseases
  can be caused by this organism

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• Rhinocerebral, pulmonary, and cutaneous diseases
  can be caused by this organism
• Zygomycosis (rhizopus spp)

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Fungal jeopardy
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• This fungus causes meningitis in AIDS patients,
  and is diagnosed by latex agglutination

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• This fungus causes meningitis in AIDS patients,
  and is diagnosed by latex agglutination
• Cryptococcus neoformans

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