Viruses Flashcards
Recombination
Exchange of genes between 2 chromosomes by crossing over within regions of significant base sequence homology
Reassortment
When viruses with segmented genomes (flu) exchange segments. High frequency recombination. Cause of worldwide influenze pandemics
Complementation
When 1 or 2 viruses that infect the cell has a mutation that results in a nonfunctional protein. The nonmutated virus “complements” the mutated one by making a functional protein that serves both viruses.
Phenotypic mixing
Occurs with simultaneous infection of a cell with 2 viruses. Genome of virus A can be partially or completely coated (forming pseudovirion) with the surface protiens of virus B. Type B protein coat determines the tropism (infectivity) of the hybrid virus. However, the progeny from this infection have a type A coat that is encoded by its type A genetic material.
Live attenuated vaccine - what response?
Types?
Induce hemoral and cell-mediated immunity but have reverted to virulence on rare occasions.
Smallpox, yellow fever, chickenpox, Sabin’s polio virus, MMR, influenza (intranasal)
Dangerous to give to IC and no booster needed
Killed vaccine
Rabies, influenza (IV), Salk Polio, HAV
Recombinant vaccine
HBV, HPV
Only ssDNA virus
Parvoviridae
All others are dsDNA
Circular DNA virus
Papilloma
Polyoma
Hepadnaviruses
All others are linear
Only dsRNA virus
Reoviridae
Positive stranded RNA viruses
retrovirus, togavirus, flavivirus, coronavirus, hepevirus, calicivirus, picornavirus (I went to a retro toga party, where I drank flavored Corona and ate hippy California pickles.
Ploidy of viruses
all viruses are haploid (1 copy of DNA or RNA) except retroviruses which have 2 identical ssRNA molecules
Where does DNA viruses replicate? RNA?
nucleus (except poxvirus)
cytoplasm (except influenza, retroviruses)
Non-enveloped viruses (Naked)
Papillomavirus, Adenovirus, Picornavirus, Polyomavirus, Calcivirus, Parvovirus, Reovirus, Hepevirus (Give PAPP (DNA) smears and CPR (RNA) to a naked Heppy)
Herpesviruses
Envelope:
Structure:
Dz: 8
Herpesviruses Envelope: yes Structure: dsDNA and linear Dz: (1) HSV1 - oral/genital lesions, temporal lobe encephalitis, keratoconjunctivitis (2) HSV2 - genital lesions (3) VSV - chickenpox, zoster (shingles) (4) EBV - mono, Burkitt's lymphoma, Hodgkin's lymphoma (5) CMV - infxn in IC patients esp transplant recipients; congenital defects (6) HHV6 - roseola (exanthem subitum) (7) HHV7 - less common cause of roseola (8) HHV8 - Kaposi's sarcoma
Hepadnavirus
Envelope:
Structure:
Dz:
Hepadnavirus
Envelope: Yes
Structure: dsDNA and partial circular
Dz: (1) HBV - acute/chronic hepatitis, vaccine available (HBV surface Ag), reverse transcriptase
Adenovirus
Envelope:
Structure:
Dz:
Adenovirus
Envelope: No
Structure: dsDNA and linear
Dz: Febrile pharyngitis (sore throat, acute hemorrhagic cystitis), pneumonia, conjunctivitis (pink eye)
Parvovirus
Envelope:
Structure:
Dz:
Parvovirus
Envelope: No
Structure: ssDNA and linear
Dz: B19 virus - aplastic crises in sickle cell disease with slapped cheeks rash in children, erythema infectiosum (fifth disease), RBC destruction in fetus leads to hydrops fetalis and death, pure RBC aplasia and rheumatoid arthritis like symptoms in adults
Papillomavirus
Envelope:
Structure:
Dz:
Papillomavirus
Envelope: No
Structure: dsDNA and circular
Dz: HPV - warts (1, 2, 6, 11), CIN/cervical cancer (16, 18); vaccine available
Polyomavirus
Envelope:
Structure:
Dz: 2
Polyomavirus
Envelope: No
Structure: dsDNA and circular
Dz: JC virus - progressive multifocal leukoencephalopathy in HIV
BK virus - transplant patients (targets kidney)
Poxvirus
Envelope:
Structure:
Dz:
Poxvirus
Envelope: Yes
Structure: dsDNA and linear (largest DNA virus)
Dz: Smallpox
Vaccinia - cowpox
Molluscum contagiosum - flesh colored dome lesions with central dimple
HSV-1
Transmission:
Dz:
HSV-1
Transmission: respiratory secretions, saliva
Dz: gingivostomatitis, keratoconjunctivitis, temporal love encephalitis (MCC sporadic encephalitis in US), herpes labialis, latent in trigeminal ganglia
HSV-2
Transmission:
Dz:
HSV-2
Transmission: Sexual contact, perinatal
Dz: Herpes genitalis, neonatal herpes, latent in sacral ganglia
VZV
Transmission:
Dz:
VZV
Transmission: respiratory secretions
Dz: varicella-zoster (chickenpox, shingles), encephalitis, pneumonia, latent in dorsal root or trigeminal ganglia
EBV
Transmission:
Dz:
Clinical:
EBV
Transmission: respiratory secretions, saliva
Dz: Infectious mono, Burkitt’s/Hodgkin’s lymphoma, nasopharyngeal carcinoma, latent in B cells
Clinical: fever, hepatosplenomegaly, pharyngitis, lymphadenopathy (posterior cervical nodes), 15-20 yoa, atypical lymphocytes on peripheral - reactive cytotoxic T cells; positive Monospot
CMV
Transmission:
Dz:
CMV
Transmission: congenital, transfusion, sexual contact, saliva, urine, transplant
Dz: congenital infxn, mono (negative monospot), pneumonia, retinitis; owl’s eye inclusions; latent in mononuclear cells
HHV-6
Dz:
HHV-6
Dz: roseola - high fevers for several days that can cause seizures, followed by a diffuse macular rash
HHV-8
Transmission:
Dz:
HHV-8
Transmission: sexual contact
Dz: Kaposi’s sarcoma (HIV patietns)
HSV diagnosis
PCR is test of choice
Tzanck test - smear of opened skin vesicle to detect multinucleared giant cell
Intranuclear Cowdry A inclusions
Reovirus Envelope: Structure: Capsid: Dz: 2
Reovirus Envelope: no Structure: dsRNA linear Capsid: icosahedral Dz: (1) coltivirus - Colorado tick fever (2) rotavirus - fatal diarrhea in children
Picornaviruses Envelope: Structure: Capsid: Dz: 5
Picornaviruses Envelope: no Structure: ssRNA linear Capsid: icosahedral Dz: (1) poliovirus - Salk/Sabin vaccine (2) echovirus - aseptic meningitis (3) Rhinovirus - common cold, acid labile so destroyed in stomach (4) Coxsackievirus - aseptic meningitis; herpangina (mouth blisters, fever); hand, food, and mouth disease, myocarditis (5) HAV - acute viral hepatitis
PERCH
Hepevirus Envelope: Structure: Capsid: Dz:
Hepevirus Envelope: No Structure: ssRNA linear Capsid: Icosahedral Dz: HEV
Caliciviruses Envelope: Structure: Capsid: Dz:
Caliciviruses Envelope: no Structure: ssRNA linear Capsid: icosahedral Dz: Norovirus - viral gastroenteritis
Flaviviruses Envelope: Structure: Capsid: Dz: 5
Flaviviruses Envelope: Yes Structure: ssRNA linear Capsid: icosahedral Dz: HCV Yellow fever Dengue St. Louis encephalitis West Nile virus
Togaviruses Envelope: Structure: Capsid: Dz: 3
Togaviruses Envelope: yes Structure: ssRNA linear Capsid: icosahedral Dz: Rubella Eastern equine encephalitis Western equine encephalitis
Retroviruses Envelope: Structure: Capsid: Dz: 2
Retroviruses Envelope: yes Structure: ssRNA linear Capsid: icosahedral (HTLV), complex&conical (HIV) Dz: HTLV - t cell leukemia HIV - AIDS
Coronaviruses Envelope: Structure: Capsid: Dz: 2
Coronaviruses Envelope: yes Structure: ssRNA linear Capsid: helical Dz: coronavirus - common cold SARS
Orthomyxoviruses Envelope: Structure: Capsid: Dz:
Orthomyxoviruses Envelope: yes Structure: ssRNA (-) linear, 8 segments Capsid: helical Dz: Influenza virus
Paramyxoviruses Envelope: Structure: Capsid: Dz: 4
Paramyxoviruses Envelope: yes Structure: ssRNA (-) linear, nonsegmented Capsid: helical Dz: Parainfluenza - croup RSV - bronchiolitis in babies give ribavirin for tx Measels Mumps
Rhabdoviruses Envelope: Structure: Capsid: Dz:
Rhabdoviruses Envelope: yes Structure: ssRNA (-) linear Capsid: helical Dz: rabies
Filoviruses Envelope: Structure: Capsid: Dz:
Filoviruses Envelope: yes Structure: ssRNA (-) linear Capsid: helical Dz: Ebola/Marburg hemorrhagic fever often fatal
Arenaviruses Envelope: Structure: Capsid: Dz: 2
Arenaviruses
Envelope: yes
Structure: ssRNA (-) circular, 2 segments
Capsid: helical
Dz: LCMV - lymphocytic choriomeningitis virus
Lassa fever encephalitis - spread by mice
Bunyaviruses Envelope: Structure: Capsid: Dz: 4
Bunyaviruses Envelope: yes Structure: ssRNA (-) circular, 3 segments Capsid: helical Dz: California encephalitis Sandfly/Rift Valley fever Crimean-Congo hemorrhagic fever Hantavirus - hemorrhagic fever, pneumonia
Delta virus Envelope: Structure: Capsid: Dz:
Delta virus Envelope: yes Structure: ssRNA (-) circular Capsid: not sure Dz: HDV - "defective" virus that requires HBV co-infection
Importance of (-) stranded viruses
must transcribe (-) to (+) - virion brings its own RNA-dependent RNA polymerase Arenaviruses Bunyaviruses Paramyxoviruses Orthomyxoviruses Filoviruses Rhabdoviruses (Always Bring Polymerase Or Fail Replication)
Segmented viruses
All are RNA Bunyaviruses Orthomyxoviruses Arenaviruses Reovirus (BOAR)
Yellow fever
flaviviruse
Aedes mosquitos (monkey or human reservoir)
high fever, black vomitus, jaundice
most important global cause of infantile gastroenteritis?
segmetned dsRNA virus - Rotavirus
acute diarrhea in US during winter esp in day-care, kindergartens
villous destruction with atrophy leads to decreased absorption of Na and loss of K
influenza
orthomyxoviruses - enveloped, (-) ssRNA with 8 segments
contain hemagglutinin (viral entry) and neuraminidase (progeny virion release) antigens
rapid genetic changes
killed viral vaccine is major mode of protection, reformulated vaccine offered each fall
genetic shift
cuases pandemics
reassortment of viral genome
segments undergo high frequency recombination, such as when human flu A virus recombines with swine flu A virus
genetic drift
causes epidemics, minor changes based on random mutation
rubella virus
togavirus
German measles - fever, postauricular adenopathy, lymphadenopathy, arthralgias, fine truncal rash that starts at head and moves down.
Mild disease in children but serious congenital disease (TORCH)
paramyxoviruses
disease in children
croup, mumps, measles, RSV (respiratory tract infection in infants)
contain surface F (fusion) protein causes respiratory epi cells to fuse and form multinucleated cells
Palivizumab (monoclonal Ab against F protein) prevents pneumonia caused by RSV infection in premature infants
measles virus
paramyxoviruse
Kopli spots (red spots with blue-white center on buccal mucosa) and descending maculopapular rash
SSPE (subacute sclerosing panencephalitis), encephalitis, giant cell pneumonia
Rash from head to toe - hands/feet
mumps viruse
paramyxovirus
Parotitis, orchitis, aseptic meningitis
can cause sterility
rabies virus
Bullet shaped virus
Negri bodies characteristic cytoplasmic inclusions in neurons infected by rabies (Purkinje cells of cerebellum - travels retrograde up nerve axons)
Weeks to months incubation
Fever, malaise –> agitation, photophobia, hydrophobia –> paralysis, coma –> death
Bat, raccoon, skunk bites
HAV Type: Transmission: Incubation: Cancer risk: Clinical:
HAV Type: RNA picornavirus Transmission: fecal-oral Incubation: short Cancer risk: No Clinical: asymptomatic, acute, no carrier
HBV Type: Transmission: Incubation: Cancer risk: Clinical:
HBV
Type: DNA hepadnavirus
Transmission: parenteral, sexual, materal-fetal
Incubation: long
Cancer risk: yes bc integrates into host genome
Clinical: carrier
HCV Type: Transmission: Incubation: Cancer risk: Clinical:
HCV
Type: RNA flavivirus
Transmission: blood, IVDU, post-transfusion
Incubation: long
Cancer risk: yes from chronic inflamm
Clinical: chronic, cirrhosis, carcinoma, carrier
HDV Type: Transmission: Incubation: Cancer risk: Clinical:
HDV
Type: RNA delta virus
Transmission: parenteral, sexual, maternal-fetal
Incubation: superinfection is short; co-infection is long
Cancer risk: yes
Clinical: defective virus that is dependent on HBV superinfection - decrease prognosis
HEV Type: Transmission: Incubation: Cancer risk: Clinical:
HEV
Type: RNA hepevirus
Transmission: fecal-oral (waterborne epidemics)
Incubation: short
Cancer risk: none
Clinical: high mortality in pregnant, enteric, expctant mothers, epidemic
Anti-HAV - IgM
IgM antibody to HAV
best test to detect active hepatitis A
Anti-HAV - IgG
IgG antibody indicates prior HAV infection and/or prior vaccination; protects against reinfection
HBsAg
Antigen found on surface of HBV; indicates hepatitis B infection
Anti-HBs
Antibody to HBsAg
Indicates immunity to hepatitis B
HBcAg
Antigen associated with core of HBV
Anti-HBc
Antibody to HBcAg
IgM - acute/recent infection
IgG - prior exposure or chronic infection
Positive during window period
HBeAg
A second, different antigenic determinant in the HBV core, HBeAg indicates active viral replication and therefore high transmissibility
Anti-HBe
Antibody to e antigen; indicates low transmissibility
viral hepatitis ALT vs AST
ALT > AST
alcoholic hepatitis ALT vs AST
AST > ALT
Acute HBV serologic markers
HBsAg, HBeAg, IgM Anti-HBc
Window period of HBV serologic markers
Anti-HBe and IgM Anti-HBc
Chronic HBV with high infectivity serologic markers
HBsAg, HBeAg, IgG Anti-HBc
Chronic HBV with low infectivity serologic markers
HBsAg, Anti-HBe, IgG Anti-HBc
Recovery from HBV serologic markers
Anti-HBs, Anti-HBe, IgG Anti-HBc
Immunized to HBV serologic markers
Anti-HBs
HIV Structure: Virulence: Immunity: Slower Course:
HIV
Structure: diploid genome (2 molecules of RNA); 3 genes (1) env from gp120 attachment to host CD5+ T cell and gp41 fusion and entry (2) gag - capsid protein (3) pol - reverse transcriptase, aspartate protease, integrase
Virulence: reverse transcriptase synthesizes dsDNA from RNA –> dsDNA integrates into host genome
Immunity: homozygous CCR5 mutation (virus binds this late) co-receptor
Slower Course: heterozygous CCR5 mutation (virus binds this early)
HIV diagnosis
Presumptive dx: ELISA (sensitive, high false positive rate and low threshold rule out test)
Western blot assay (specific, high false negative rate and high threshold, rule in test)
Both look for antibodies to viral proteins - falsely neg in first 1-2 months of HIV infection and falsely positive initially in babies born to infected mothers
HIV prognostic test
PCR/viral load test - amount of viral RNA in the plasma
High viral load associated with poor prognosis
Also used to monitor effect of drug therapy
AIDS Dx
diagnosis <1.5
- flu-like (acute)
- feeling fine (latent)
- falling count
- final crisis
Immunocompromised CD4
<400 CD4+ cell/mm3
AIDS-defining illnesses emerge
<200 CD4+ cells/mm3
Systemic disease of HIV +
Low grade fevers, cough, hepatosplenomegaly, tongue ulcer
Oval yeast cells w/i macrophages
CD4 < 100
Histoplasma capsulatum (usually just pulmonary sx in healthy)
Dermatologic disease of HIV +
Fluffy white cottage-cheese lesions: pseudohyphae, commonly oral if CD4 C. albicans
Superficial vascular proliferation: PMN inflammation –> Bartonella henselae (bacillary angiomatosis)
Gastrointestinal disease of HIV +
Chronic, watery diarrhea: acid fast cysts seen in stool when CD4 < 200 –> Cryptosporidum
Encephalopathy of HIV +
reactivation of latent virus –> demyelination (CD4 < 200) –> JC virus reactivation (PML)
Abscesses of HIV +
Many ring enhancing lesions on imaging, CD4 Toxoplasma gondii
Meningitis of HIV +
India ink stain reveals yeast with narrow based budding and large capsule, CD4 < 50 –> cryptococcus neoformans
Retinitis of HIV +
Cotton wool spots on funduscopic exam and may also occur with esophagitis, CD4 < 40 –> CMV
Dementia of HIV +
Directly associated with HIV
Oncologic disease of HIV +
HHV-8 (Kaposi’s sarcoma): biopsy reveals lymphocytic inflamm –> superficial neoplastic proliferation of vasculature
EBV: lateral tongue –> hairy leukoplakia
EBV: oropharynx (Waldeyer’s ring) –> Non-Hodgkin’s lymphoma (large cell type)
HPV: often in anus or cervix –> SCC
EBV: focal or multiple –> primary CNS lymphoma
Respiratory diseases of HIV +
CMV –> biopsy reveals cells with intranuclear (owl’s eye) inclusion bodies –> interstitial pneumonia
Aspergillus fumigatus –> pleuritic pain, hemoptysis, infiltrates on imaging –> invasive aspergillosis
Pneumocystis jirovecii –> CD4 Pneumonia
Mycobacterium avium-intracellulare –> CD4 tuberculosis like disease
Prions
Mutation?
Presentation?
Types?
Caused by conversion of a normal cellular protein termed prion protein (PrPc) to a beta-pleated form (PrPsc) which is transmissible.
PrPsc resists degradation and facilitates the conversion of still more PrPc to PrPsc.
Spongiform encephalopathy and dementia, ataxia, and death.
Creutzfeldt-Jakob diseae = sporadic with rapidly progressive dementia
Gerstmann-Straussler-Scheinker syndrome = inherited
Kuru = acquired
Prions
Mutation?
Presentation?
Types?
Caused by conversion of a normal cellular protein termed prion protein (PrPc) to a beta-pleated form (PrPsc) which is transmissible.
PrPsc resists degradation and facilitates the conversion of still more PrPc to PrPsc.
Spongiform encephalopathy and dementia, ataxia, and death.
Creutzfeldt-Jakob diseae = sporadic with rapidly progressive dementia
Gerstmann-Straussler-Scheinker syndrome = inherited
Kuru = acquired
