Recombination
exchange of genes between 2 chromosomes by crossing over within regions of significant base sequence homology
Reassortment
when viruses with segmented genomes (influenza) exchange segments
Compementation
when 1 of 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
simultaneous infection of a cell with 2 viruses; genome of virus A can be partially or completely coated with the surface proteins of virus B. Type B protein coat determines the tropism of the hybrid virus but the progeny have a type A coat encoded by the type A genetic material
Live attenuated viruses induce…
humoral and cell-mediated immunity but have reverted to virulence on occasion. No booster needed.
Killed/inactivated viruses induce….
only humoral immunity but are stable.
Live attenuated vaccines (6)
- smallpox
- yellow fever
- chickenpox
- Sabin polio virus
- MMR
- influenza (intranasal)
Killed vaccines (4)
- Rabies
- Influenza (injected)
- Salk Polio
- HAV
Recombinant vaccines (2)
- HBV
2. HPV
All DNA viruses are dsDNA except…
parvoviridae.
All DNA viruses are linear except…
papilloma, polyoma and hepadna (which are circular).
All RNA viruses are ssRNA excpet…
Reoviridae.
Positive stranded RNA viruses (7)
Retrovirus Togavirus Flavivirus Coronavirus Hepevirus Calicivirus Picornavirus
Purified nucleic acids of most dsDNA and + strand ssRNA viruses are…
infectious.
Naked nucleic acids of - strand ssRNA and dsRNA viruses are…
not infectious. They require polymerases conatined in the complete virion.
DNA viruses replicate in…
the nucleus, except poxvirus.
RNA viruses replicate in…
the cytoplasm, except influenza and retroviruses).
Nake viruses include:
papillomavirus adenovirus parvovirus polyomavirus calicivirus picornavirus reovirus hepevirus
Generally, viruses acqurie an envelope from…
plasma membrane when they exit a cell.
exception: herpesvirus acquires its envelope from the nuclear membrane
DNA viruses (7)
HHAPPPP(y)
- Hepadna
- Herpes
- Adeno
- Pox
- Parvo
- Papilloma
- Polyoma
DNA viruses general rules (4):
- are double stranded
- are linear
- are icosahedral
- replicate in the nuclus
The DNA virus that is not double stranded is…
parvovirus.
The DNA viruses that are not linear are…
papillomavirus/polyomavirus (circular, supercoiled) and hepadnavirus (circular, incomplete).
The DNA virus that is not icosahedral is…
poxvirus.
The DNA virus that does not replicate in the nucleus is…
poxvirus (it carries its own DNA-dependent RNA polymerase).
DNA viruses w/ an envelope
- herpesvirus
- hepadnavirus
- poxvirus
HBV features
- hepadnavirus
- hepatitis (acute or chronic)
- vaccine (contains surface Ag)
- not a retrovirus but has reverse transcriptase
Adenovirus medical importance
- febrile pharyngitis (sore throat)
- acute hemorrhagic cystitis
- pneumonia
- conjunctivitis (“pink eye”)
Parvovirus features (4)
- B19 virus: aplastic crises in sickle cell
- “slapped cheeks” rash in children: eythema infectiosum (fifth disease)
- RBC destructino in fetus leads to hydrops fetalis and death
- pure RBC aplasia/RA-like symptoms in adults
Papillomavirus features
HPV: warts (1,2,6,11)
CIN
Cervical cancer (16, 18)
Polyomavirus features
JC virus: PML in HIV
BK virus: transplant pts, commonly targets the kidney
Poxvirus features
- smallpox (potential warfare)
- cowpox (milkmaid blisters)
- molluscum contagiosum (flesh-colored dome lesions with central umbilicated dimple)
HSV-1 diseases (4)
- gingivostomatitis
- keratoconjunctivitis
- temporal lobe encephalitis
- herpes labialsi
HSV-1 is latent in the…
trigeminal ganglia.
HSV-1 is transmitted via….
respiratory secretions and saliva.
HSV-2 diseaes
- herpes genitalis
- neonatal herpes
HSV-2 is latent in the…
sacral ganglia.
HSV-2 is transmitted by…
respiratory secretions.
VZV diseases
- chicken pox
- shingles
- encephalitis
- pneumonia
VZV is latent in the…
dorsal root or trigeminal ganglia.
Most common complication of shingles is…
post-herpetic neuralgia.
VZV is transmitted by…
respiratory secretions.
EBV causes…
mononucleosis which is characterized by fever, hepatosplenomegaly, pharyngitis and lymphadenopathy (esp. posterior cervical nodes).
Transmitted by respiratory secretions/saliva. Commonly seen in teens/YAs.
EBV infects…
B cells. But the atypical lymphocytes seen on peripheral blood smear are not infected B cells but rather reactive cytotoxic T cells.
EBV is detected by…
positive monospot test - heterophile antibodies detected by agglutination of sheep/horse RBCs.
EBV is associated with…
Hodgkin lymphoma, endemic Burkitt lymphoma and nasopharyngeal carcinoma.
CMV causes…
- congenital infection
- mononucleosis (negative monospot)
- pneumonia
- retinitis
CMV infected cells have…
characteristic “owl eye” inclusions.
CMV is latent in…
mononuclear cells.
CMV is transmitted…
congenitally and by transfusion, sexual contact, saliva, urine and transplant.
HHV-6 causes….
Roseola: high fevers for several days that can cause seizures, followed by a diffuse macular rash.
(transmitted by saliva)
HHV-8 causes…
Kaposi sarcoma, a neoplasm of endothelial cells.
transmitted by sexual contact
Kaposi sarcoma is seen in…
HIV/AIDS and transplant pts.
Kaposi sarcoma presents with…
dark/violaceous flat and nodular skin lesions representing endothelial growths. It can also effect GI tract and lungs.
HSV Identification
- viral culture for skin/genitalia
- CSF PCR for herpes encephalitis
- Tzanck test
The Tzanck smear is a…
smear of opened skin vesicles (from genital herpes) to detect multinucleated giant cells.
HSV infected cells also have…
intranuclear Cowdry A inclusions.
Reovirus features
Envelope: No
RNA structure: DS linear, 10-12 segments
Capsid: icosahedral (double)
Reovirus disease
- coltivirus = colorado tick fever
2. rotavirus = #1 cause of fatal diarrhea in children
Picornavirus features
Envelope: No
RNA structure: SS + linear
Capsid: icosahedral
Picornavirus disease
- Poliovirus - Salk/Sabin vaccines
- Echovirus = aseptic meningitis
- Rhinovirus = common cold
- Coxsackievirus = aseptic meningitis; herpangina; hand, foot and mouth disease; myocarditis, pericarditis
- HAV = acute viral hepatitis
Hepevirus features
Envelope: No
RNA structure: SS+, linear
Capsid: Icosahedral
Hepevirus disease
HEV
Calicivirus features
Envelope: No
RNA structure: SS + linear
Capsid: Icosahedral
Calicivirus disease
Norovirus = viral gastroenteritis
Flaviviruses features
Envelope: Yes
RNA structure: SS + linear
Capsid: icosahedral
Flaviviruses diseases
- HCV
- Yellow fever
- Dengue
- St. Louis encephalitis
- West Nile virus
Togavirus features
Envelope: Yes
RNA structure: SS+, linear
Capsid: Icosahedral
Togavirus diseases
- Rubella
- Eastern equine encephalitis
- Western equine encephalitis
Retroviruses features
Envelope: Yes
RNA structure: SS+, linear
Capsid: Icosahedral (HTLV), complex and conical (HIV)
(have reverse transcriptase)
Retrovirus diseaes
- HTLV = T-cell leukemia
2. HIV = AIDS
Coronaviruses features
Envelope: Yes
RNA structure: SS+, linear
Capsid: helical
Coronavirus disease
Coronavirus = “common cold” and SARS
Orthomyxoviruses features
Envelope: Yes
RNA structure: SS+, linear
Capsid: helical
Orthomyxovirus disease
influenza virus
Paramyxovirus features
Envelope: Yes
RNA structure: SS-, linear, nonsegmented
Capsid: helical
Paramyxovirus disease
- Paramyxovirus = croup
- RSV = broncholitis in babies
- Measles/Mumps
Rhabdoviruses features
Envelope: Yes
RNA structure: SS-, linear
Capsid: Helical
Rhabdovirus disease
Rabies
Filovirus features
Envelope: Yes
RNA structure: SS-, linear
Capsid: helical
Filoviruses Diseases
Ebola/Marburg hemorrhagic fever
Arenaviruses features
Envelope: Yes
RNA structure: SS-, circular, 2 segments
Capsid: Helical
Arenaviruses diseases
- LCMV = lymphocytic choriomeningitis virus
2. Lassa fever encephalitis = spreads by mice
Bunyaviruses features
Envelope: Yes
RNA structure: SS-, circular, 3 segments
Capsid: helical
Bunyaviruses diseases
- California encephalitis
- Sandfly/Rift Valley fevers
- Crimean-Congo hemorrhagic fever
- Hantavirus = hemorrhagic fever, pneumonia
Delta virus features
Envelope: Yes
RNA structure: SS-, circular
Capsid: uncertain
Delta virus disease
HDV is a “defective” virus that requires HBV co-infection.
Negative stranded viruses must…
transcribe negative strand to positive. The virion brings its own RNA-dependent RNA polymerase.
Negative stranded viruses include (6):
- Arenaviruses
- Bunyaviruses
- Paramyxoviruses
- Orthomyxoviurses
- Filoviruses
- Rhabdoviruses
(Always Bring Polymerase Or Fail Replication)
Segmented viruses are all…
RNA viruses:
- Bunyaviruses
- Orthomyxoviruses
- Arenaviruses
- Reoviruses
(BOAR)
Picornaviruses have RNA that is translated into…
1 large polypeptide that is cleaved by proteases into functional viral proteins.
All picornoviruses can casuse aseptic meningitis except…
rhinovirus and HAV.
All picornaviruses are enteroviruses which means…
fecal-oral spread. Except for rhinovirus.
Features of rhinovirus
-acid labile (destroyed by the stomach acid) and therefore does not infect GI like other picornaviruses
Yellow fever virus is a flavivirus (also an arbovirus) transmitted by…
the Aedes mosquitoes. The virus has a monkey or human reservoir.
Yellow fever virus symptoms include…
high fever, black vomitus and jaundice.
Rotavirus is the major cause of…
acute diarrhea in the US during winter, esp. in day-cars, kindergartens. It causes villous destruction witha trophy leading to decreased absorption of Na+ and loss of K+.
Influenza virus contains…
hemagglutinin (promotes viral entry) and neuraminidase (promotes progeny virion release) antigens. Has rapid genetic changes.
Influenza virus puts pts at risk for…
fatal bacterial superinfection.
Genetic shift/antigenic shifts casues…
pandemics. It is reassortment of the viral genome.
During genetic shift, segmetns undergo…
high-frequency recombination, such as when human flu A virus recombines with swine flu A virus.
Genetic drift causes…
epidemics. Minor changes are based on random mutation.
Rubella causes…
fever, postauricular and other lymphadenopathy, arthralgias and fine rash. It is mild in children but serious congenitally.
Congenital rubella findings include…
“blueberry muffin” appearance, indicative of extramedullary hematopoiesis.
All paramyxoviruses contain…
F (fusion) protein, which causes respiratory epithelial cells to fuse and form multinucleated cells.
Palivizumab is a…
monoclonal antibody against F protein that prevents pneumonia caused by RSV infection in premature infants.
Measles characteristic signs are…
Koplik spots and descending maculopapular rash.
Koplik spots are…
bright red spots with blue-white center on buccal mucosa that precede the measles rash by 1-2 days.
Possible sequelae of Measles are…
- Subacute sclerosing panencephalitis (SSPE)
- Encephalitis
- Giant cell pneumonia
SSPE symptoms
behavior changes, myoclonus, ataxia, ocular abnormalities, coma, increased Igs in CSF
3 C’s of Measles
Cough
Coryza
Conjunctivitis
When infected with the mesles virus, Vitamin A is used to…
prevent severe exfoliative dermatitis in malnourished children.
Symptoms of Mumps
- Parotitis
- Orchitis
- aseptic Meningitis
-can cause sterility
Rabies virus features
- bullet-shaped
- Negri bodies (in purkinje cells and hippocampus)
Postexposure treatment for rabies is…
wound cleansing and vaccination +/- rabies immune globulin.
Rabies virus travels to…
the CNS by migrating in a retrograde fashion up nerve axons.
Progression of rabies disease:
fever/malaise -> agitation/photophobia/hydrophobia -> paralysis/coma -> death
Rabies virus in the US is most commonly from…
bat, raccoon and skunk bites.
HAV features
- RNA picornavirus
- fecal-oral transmission
- no carrier
- short incubation (wks)
- no HCC risk
HBV features
- DNA hepadnavirus
- parenteral, sexual, maternal-fetal transmission
- yes carrier
- long incubation
- HCC risk bc it integrates into host genome and acts as an oncogene
- HBV can cause carcinoma w/o cirrhosis!
HCV features
- RNA flavivirus
- blood transmission (IVDU, transfusion)
- yes carrier
- long incubation
- HCC risk because of chronic inflammation
HDV feature
- RNA delta virus
- parenteral, sexual, maternal-fetal transmission
- yes carrier
- superinfection (HDV after HBV) short incubation
- coinfection (HDV with HBV) long incubation
- HCC risk
HEV features
- RNA hepevirus
- fecal-oral transmission
- no carrier
- short incubation
- no HCC risk
- high mortality in pregnant mothers
In HBV, the DNA polymerase has both….
DNA and RNA dependent activities. UPon entry into the nucleus, the polymerase functions to complete the partial dsDNA. The host RNA polymerase transcribes mRNA from viral DNA to make viral proteins. The DNA polymerase then reverse transcribes viral RNA to DNA to make new viral particles.
Anti-HAV (IgM)
IgM antibody to HAV; best test to detect active hep A
Anti-HAV (IgG)
IgG antibody indicates prior HAV infection and/or prior vaccination; protects against reinfection
HBsAg
Ag found on surface of HBV; indicates Hep B infection
HBcAg
antigen associated with core of HBV (indicates actual infection rather than immunization)
Anti-HBc
antibody to HBcAg; IgM = acute/recent infxn; IgG = prior exposure or chornic 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 HBeAg; indicates low transmissibility
ALT > AST indicates…
viral hepatitis.
AST > ALT indicates…
alcoholic hepatitis.
The 3 structural genes of HIV are…
- env (gp120 and gp41)
- gag (p24) - capsid protein
- pol (reverse transcriptase, aspartate protease, and integrase
Env is formed from…
cleavage of gp160 to form envelope glycoproteins.
gp120 is for…
attachement of HIV to host CD4+ T cell.
gp41 is for…
fusion and entry.
HIV dsDNa is able to…
integrate into host genome.
The HIV virus binds…
CCR5 or CXCR4 co-receptor and CD4 on T cells. It binds CCR5 and CD4 on macrophages.
Homozygous CCR5 mutation gives…
immunity to HIV. Heterozygous mutation causes a slower course.
A presumptive diagnosis of HIV is made with…
ELISA (sensitive, high false-positive rate and low threshold).
+ ELISA for HIV is then confirmed with…
Western blot assay (specific, high false-negative rate and high threshold).
AIDS diagnosis is…
less than 200 CD4+ cells.
ELISA/Western blot tests look for…
antibodies to viral proteins; these are often falsely negative in the first 1-2 months of HIV infection and falsely positive in babies born to infected mothers because anti-gp120 crosses the placenta.
During the latent phase of HIV, the virus…
replicates in LNs.
Prion diseases are caused by…
the conversion of a normal (predominantly alpha-helical) prion protein (PrPc) to a beta-pleated sheet form (PrPsc) which is transmissible.
PrPsc resists…
protease degradation and facilitates the conversion of still more PrPc to PrPsc.
Accumulation of PrPsc results in…
spongiform encephalopathy and dementia, ataxia and death.
Types of Prion Disease
- Creutzfeldt-Jacob disease (sporadic, rapidly progressive dementia)
- Gerstmann (inherited)
- Kuru (acquired)
