Microbiology: Viruses

• -naked with icosahedral capsid
• -enveloped with icosahedral capsid
• -enveloped with helical capsid

Enveloped viruses can have surface proteins

1. Recombination: crossing over of chromosomes

2. Reassortment: exchange of segments, worldwide flu pandemics

3. Complementation: 1 of 2 viruses infecting a cell has a mutation that results in non-functional protein but non-mutated virus makes a functional protein for both

4. Phenotypic Mixing: in cells simultaneously infected with two viruses, can have mixed coating of viruses determining tropism

"Live! One night only! See small yellow chickens get vaccinated with Sabin's and MMR! It's incredible!"

• -Smallpox
• -Yellow Fever
• -Chickenpox (VZV)
• -Sabin's Polio
• -MMR
• -Influenza (intranasal)

• -no booster needed for live attenuated
• -dangerous to give to immunocompromised or close relatives

"RIP Always"

• Rabies
• Influenza (injected)
• Polio (Salk = Killed)
• HAV

• HBV (recombinant HBsAg)
• HPV (types 6, 11, 16, 18)

-all DNA viruses are double stranded except: PARVOVIRUS = "part-of-a-virus"

-all DNA viruses are linear except: papilloma, polyoma and hepadnaviruses

-all RNA viruses are ssRNA except: REOVIRUS "like a river"

"I went to a retro toga party, where I drank flavored Corona and ate hippy California pickles"

• Retrovirus
• Togavirus
• Flavivirus
• Coronavirus
• Hepevirus
• Calicivirus
• Picornavirus

"Always Bring Polymerase Or Fail Replication"

• Arenavirus
• Bunyavirus
• Paramyxovirus
• Orthomyxovirus
• Filovirus
• Rhabdovirus

virion brings own RNA-dependent RNA pol

• INFECTIOUS:
• -purified nucleic acid from dsDNA viruses (except poxvirus and HBV)
• -purified nucleic acid from + ssRNA viruses

• NOT INFECTIOUS:
• -purified nucleic acids of - ssRNA and dsRNA viruses (require polymerases)

-all viruses are haploid except retrovirus (diploid)

• -all in nucleus
• -EXCEPT poxvirus

• -all replicate in cytoplasm
• -EXCEPT influenza and retroviruses

"Give PAPP smears and CPR to a naked Heppy"

• PAPP=DNA
• CPR + Hepe = RNA

• Papillomavirus
• Adenovirus
• Picornavirus
• Polyomavirus

• Calcivirus
• Parvovirus
• Reovirus
• Hepevirus

• -generally from plasma membrane
• -EXCEPT: herpesviruses (nuclear membrane)

"are HHAPPPPy viruses!"

• Hepadna
• Herpes
• Adeno
• Parvo
• Pox
• Papilloma
• Polyoma

• Structure:
• -enveloped
• -dsDNA, linear

• HSV1
• HSV2
• VZV
• EBV
• CMV
• HHV6
• HHV7
• HHV8

• Diseases:
• -Gingivostomatitis
• -keratoconjunctivitis
• -temporal lobe encephalitis
• -labial herpes
• 

• Latent in:
• -Trigeminal ganglia

• Transmission:
• -respiratory secretions
• -saliva

• Diseases:
• -genital herpes
• -neonatal herpes
• 

• Latent in:
• -sacral ganglia

• Transmission:
• -sexual contact
• -perinatal

• Diseases:
• -Varicella Zoster (chicken pox, shingles)
• -encephalitis
• -pneumonia
• 

• Latent in:
• -Dorsal Root Ganglia
• -Trigeminal ganglion

• Transmission:
• -respiratory secretions

• Diseases:
• -mononucleosis
• -Burkitt's/Hodgkin's lymphoma
• -nasopharyngeal carcinoma

• Presentation:
• -fever
• -HSM
• -pharyngitis
• -lymphadenopathy (post cervical)

• Epidemiology:
• -15-20 years

• Diagnosis:
• -atypical lymphocytes on blood smear (CTLs) "hugging RBCs"
• 
• -positive Monospot (Abs detected by agglutination of sheep or horse RBCs)

• Latent in:
• -B cells

• Transmission:
• -respiratory secretions
• -saliva

***infection in immunosuppressed patients

• Diseases:
• -congenital infection --> defects
• -mononucleosis (negative monospot)
• -pneumonia
• -AIDs retinitis

• Latent in:
• -mononuclear cells

• Transmission:
• -Congenital
• -transfusions
• -sexual contact
• -urine
• -transplant

• "owl's eye inclusions"
• 
• "sightomegalovirus"

• Diseases:
• -Roseola (high fevers that may cause seizures, diffuse macular rash)

• Transmission:
• -not determined

• Diseases:
• -Kaposi's Sarcoma in HIV patients

• Transmission:
• -sexual contact

-PCR

• -Tzanck test: smear of vesicle to detect multinucleated giant cells (HSV1, HSV2, VZV)
• "Tzanck heavens I don't have herpes!"

-Intranuclear Cowdry A inclusions

• Structure:
• -Enveloped
• -ds DNA
• -partially circular

• HBV
• -acute or chronic hepatitis
• -vaccine available
• -not a retrovirus but has reverse transcriptase (treatment)

• Structure:
• -enveloped
• -ds DNA
• -linear

• Diseases:
• -Febrile pharyngitis: sore throat, acute hemorrhagic cystitis
• -Pneumonia
• -Conjunctivitis

• Structure:
• -enveloped
• -ss DNA
• -linear
• ***smallest DNA virus

• B19 Virus
• -aplastic crisis in Sickle Cell, "slapped cheek" rash in kids
• -erythema infectiosum (fifth disease)
• -RBC destruction in fetus leads to hydrops fetalis and death
• -pure RBC aplasia and RA-like sx in adults
• 

• Structure:
• -enveloped
• -ds DNA
• -circular

• HPV
• -genital warts (1, 2, 6, 11)
• -CIN, cervical cancer (16, 18)

Vaccine available

• Structure:
• -enveloped
• -dsDNA
• -circular

• JC Virus
• -progressive multifocal leukoencephalopathy (PML) in HIV patients

• BK Virus
• -transplant patients
• -commonly targets kidneys

"JC: Junky cerebrum, BK: Bad Kidneys"

• Structure:
• -Enveloped
• -ds DNA
• -linear
• ***largest DNA virus

• Smallpox
• -eradicated, may be used in germ warfare

• Vaccinia
• -cowpox ("milkmaids' blisters")

• Molluscum contagiosum
• -flesh colored dome lesions with central dimple

• Reovirus
• Picornavirus
• Hepevirus
• Calicivirus
• Flavivirus
• Togavirus
• Retrovirus
• Coronavirus
• Orthomyxovirus
• Paramyxovirus
• Rhabdovirus
• Filovirus
• Arenavirus
• Bunyavirus
• Delta virus

• Structure:
• -non-enveloped, icosahedral
• -ds RNA
• -linear
• -segmented (10-12)

• Coltivirus:
• -Colorado tick fever

• Rotavirus:
• -#1 cause of fatal diarrhea in children

• -most important global cause of infantile gastroenteritis
• -major cause of acute diarrhea in the US during winter
• -esp day care centers, kindergartens

• Pathophysiology:
• -villous destruction with atrophy
• -causes decreased absorption of Na and loss of K

• Structure:
• -non-enveloped, icosahedral
• -(+) ssRNA
• -linear

• "PERCH"
• Poliovirus: vaccine
• Echovirus: aspectic meningitis
• Rhinovirus: common cold
• Coxsackievirus: aseptic meningitis, herpangina, hand foot and mouth disease, myocarditis
• HAV: acute viral hepatitis

• -RNA is translated into 1 large polypeptide
• -cleaved by proteases

Cause: aseptic meningitis (except rhino and HAV)

All are enteroviruses --> F/O transmission (except rhino)

• -common cold
• ->100 serologic types
• -acid labile (destroyed by stomach acid) --> doesn't infect the GI tract like the other picornaviruses

• Structure:
• -non-enveloped, icosahedral
• -(+) ssRNA
• -linear

HEV

• Structure:
• -non-enveloped, icosahedral
• -(+) ssRNA
• -linear

Norovirus: gastroenteritis

• Structure:
• -enveloped, icosahedral
• -(+) ssRNA
• -linear

• HCV
• Yellow Fever
• Dengue
• St. Louis encephalitis
• West Nile Virus

Arboviruses: Yellow fever, dengue, st louis encephalitis, west nile virus

-arbovirus: transmitted by mosquites (Aedes)

Reservoir: humans or monkeys

• Symptoms:
• -high fever
• -black vomitus
• -jaundice

"flavi = yellow --> jaundice"

• Structure:
• -enveloped, iscosahedral
• -(+) ssRNA
• -linear

• Rubella
• Eastern equine encephalitis
• Western equine encephalitis

• -"German measles"
• -3 days

• Symptoms:
• -fever
• -postauricular adenopathy
• -lymphadenopathy
• -arthralgias
• -fine truncal rash that starts and head and moves down
• -causes mild disease in children
• -serious congenital disease

-ToRCHeS infection

• Structure:
• -enveloped, icosahedral/complex and conical
• -(+) ssRNA
• -linear

***have reverse transcriptase

• HTLV: T cell leukemia
• HIV: AIDS

• Structure:
• -Enveloped, helical
• -(+) ssRNA
• -linear

• -"common cold"
• -SARS

• Structure:
• -enveloped, helical
• -(+) ssRNA, linear
• -segmental (8)

Influenza virus

• -hemagglutinin: viral entry
• -neuraminidase: progeny viral release

Patients at risk for fatal bacterial superinfection (post flu pneumonia)

Rapid genetic changes

Antigenic shift and drift

• -causes pandemics
• -reassortment of viral genome

EG: human flu A recombines with swine flu A

"Sudden shift is more deadly than gradual drift"

-causes epidemics

-minor changes based on random mutation

• Structure:
• -enveloped, helical
• -(+) ssRNA
• -linear

• Parainfluenza: Croup
• RSV: bronchiolitis in babies (Rx = ribavirin)
• Measles, Mumps

Paramyxovirus

-surface F protein: causes respiratory epithelial cells to fuse and form multinucleated cells

Palivizumab (monoclonal Ab against F protein): prevents pneumonia caused by RSV in preemies

• Symptoms:
• -Koplik spots: red spot with blue-white center on buccal mucosa
• -descending maculopapular rash (presents last)
• 
• 

• Possible sequelae:
• -SSPE (subacute sclerosing panencephalitis, years later)
• -encephalitis
• -pneumonia (in immunosuppressed)

***rash includes hands and feet (vs rubella)

• 3 Cs of measles:
• -Cough
• -Coryza
• -Conjunctivitis

• Symptoms:
• -Parotitis
• -Orchitis
• -aspetic Meningitis
• 

"Mumps makes your parotid glands and testes as big as POM-poms"

***can cause sterility

• Structure:
• -enveloped, helical
• -(-) ssRNA
• -linear

Rabies

• -bullet shaped
• -Negri bodies: cytoplasmic inclusions
• 

• Pathphysiology:
• -infects neurons (Purkinje cells in cerebellum)
• -travels to CNS by retrograde travel up nerve axons

-long incubation period (weeks to months)

• Symptoms:
• -fever
• -malaise
• -agitation
• -photophobia
• -hydrophobia
• -paralysis
• -coma
• -death

• Treatment:
• -wound cleansing
• -vaccination +/- rabies Ig

**in US from bat, racoon, skunk bites

• Structure:
• -enveloped, helical
• -(-) ssRNA
• -linear

• Ebola
• Marburg hemorrhagic fever

OFTEN FATAL!!!

• Structure:
• -enveloped, helical
• -(-) ssRNA
• -circular
• -2 segments

• LCMV
• Lassa fever encephalitis (spread by mice)

• Structure:
• -enveloped, helical
• -(-) ssRNA
• -circular
• -3 segments

• California encephalitis
• Sandfly/Rift Valley fevers
• Crimean-Congo hemorrhagic fever
• Hantavirus (hemorrhagic fever, pneumonia)

• Structure:
• -enveloped, uncertain
• -(-) ssRNA
• -circular

HDV: "defective virus" that requires HBV co-infection

"Can't have Doggie without the Boyfriend"

"The vowels hit your bowels": HAV and HEV are F/O

• Episodes of:
• -fever
• -jaundice
• -elevated AST, ALT

ALT > AST (vs alcoholic hepatitis, AST>ALT)

Virus: RNA picorna

Transmission: F/O

Carrier: No

Incubation: short (weeks)

HCC Risk: No

Asymptomatic, Acute, Alone (no carriers)

Virus: DNA hepadna

Transmission: parenteral, sexual, maternal-fetal

Carrier: Yes

Incubation: Long (months)

HCC Risk: Yes (integrates into genome, acts as oncogene)

Virus: DNA flavivirus

Transmission: blood (IVDU), post transfusion

Carrier: Yes

Incubation: Long

HCC Risk: Yes from chronic inflammation

Chronic, Cirrhosis, Carcinoma, Carrier

Virus: RNA delta virus

Transmission: Parenteral, sexual, maternal-fetal

Carrier: yes

Incubation: Superinfection (short), co-infection (long)

HCC Risk: yes

• Defective virus, Dependent on HBV
• superinfection --> worse prognosis

Virus: RNA hepevirus

Transmission: F/O

Carrier: No

Incubation: Short

HCC Risk: No

**High mortality in pregnant women

Enteric, Expectant mothers, Epidemic

-best test to detect active hepatitis A

-indicates prior HAV infection and/or prior vaccination

-protects against reinfection

• -found on the surface of HBV
• -indicates hepatitis B infection

-indicates immunity to hepatitis B

-antigen associated with core of HBV

• -IgM = acute/recent infection
• -IgG = prior exposure or chronic infection

-Positive during window period

• -different antigen in HBV core
• -indicates active viral replication and high transmissibility

-indicates low transmissibility

• SECES
• -SE are antigens
• -CES are antibodies
• -in order of appearance

-diploid genome (2 RNAs)

• Genes and Proteins
• 1. env --> gp120 and gp41
•      -gp120: attach to CD4 cells
•      -gp41: fusion and entry
• 2. gag --> (p24)
•      -capsid protein
• 3. pol
•      -RT
•      -aspartate protease
•      -integrase
• 

• 
• Virus binds CCR5 (early) or CXCR4 (late) on CD4 cells/CCR5 and CD4 on macrophages

RT synthesizes dsDNA from RNA --> integration

HIV binds CCR5 on CD4 cells and macrophages

• Homozygous CCR5 mutation: immunity
• Heterozygous CCR5 mutation: slower course

• 1. ELISA ("rule out" test)
• -sensitive
• -high false positive rate
• -low threshold

• 2. Western blot assay ("rule in" test)
• -specific
• -high false negative rate
• -high threshold

• 3. HIV PCR/Viral Load
• -amount of viral RNA in plasma
• -monitor effect of drug therapy

• **ELISA and Western blot look for antibodies to viral proteins
• **May be falsely negative in first 1-2 months of infection
• **May be falsely positive in babies born to infected mothers

• 1. <200 CD4 cells/mm³
• 2. HIV⁺ with AIDS defining condition or CD4/CD8 ration <1.5

• Red = CD4 count
• Blue = HIV RNA

• "Four stages of infection:
• 1. Flu-like (acute)
• 2. Feeling fine (latent)
• 3. Falling count
• 4. Final crisis"

**during latent phase virus replicates in lymph nodes

• 1. Systemic
•      -Histoplasma capsulatum (pulm sx)

• 2. Dermatologic
•      -C. albicans (thrush)
•      -Bartonella henselae (bacillary angiomatosis)

• 3. GI
•      -Cryptosporidium

• 4. Neuro
•      -JC virus reactivation (PML)
•      -Toxoplasma (abscesses)
•      -Cryptococcus neoformans (meningitis)
•      -CMV (retinitis)

• 5. Oncologic
•      -Kaposi's Sarcoma (HHV8)
•      -Hairy Leukoplakia (EBV)
•      -Non-Hodgkin's lymphoma (maybe EBV)
•      -Squamous cell carcinoma (HPV)
•      -CNS lymphoma (often associated with EBV)

• 6. Respiratory
•      -Interstitial pneumonia (CMV)
•      -Aspergillus
•      -pneumocystis jirovecii (pneumonia)
•      -mycobacterium avium-intracellulare

• Sx:
• -low grade fevers
• -cough
• -HSM
• -tongue ulcer

• Findings:
• -oval yeast cells within macrophages

CD4 count <100

**in immunocompetent hosts only causes pulmonary sx

• Sx:
• -fluffy white cottage cheese lesions
• -thrush

• Findings:
• -pseudohyphae

• CD4 count <400 --> oral
• CD4 count <100 --> esophageal

• Sx:
• -superficial vascular proliferation
• -bacillary angiomatosis

• Findings:
• -bx: neutrophilic inflammation

• Sx:
• -chronic watery diarrhea

• Findings:
• -acid-fast cysts in stool

CD4 count <200

• Sx:
• -encephalopathy
• -viral reactivation --> demyelination

CD4 <200

• Sx:
• -brain abscesses

• Findings:
• -many ring-enhancing lesions on imaging

CD4 <100

• Sx:
• -meningitis

• Findings:
• -India ink stain reveals yeast with narrow-based budding and large capsule

CD4 count <50

• 1. Neurologic
• Sx:
• -Retinitis
• Findings:
• -cotton wool spots on fundoscopy

CD4 count <50

• 2. Respiratory
• Sx:
• -interstitial pneumonia
• Findings:
• -bx: reveals cells with intranuclear "owl's eye" inclusions

• Sx:
• -superficial neoplastic proliferation of vasculature

• Findings:
• -bx: lymphocytic infiltration

***DON'T confuse with bacillary angiomatosis

-Hairy leukoplakia

• Maybe associated with:
• -Non-Hodgkin's lymphoma (often in oropharynx)
• -Primary CNS lymphoma

• Sx:
• -invasive aspergillosis (pulm)

• Findings:
• -pleuritic pain
• -hemoptysis
• -infiltrates on imaging

• Sx:
• -pneumonia

Esp with CD4 count <200

• Sx:
• -TB-like disease

Esp with CD4 count <50