USMLE - Micro Viruses

Viruses with segmented genomes exchange segments
High frequency re-combination
Worldwide pandemics
Influenza virus

1 of 2 viruses that infects a cell has a mutation that results in a nonfunctional protein. The non-mutated virus complements the mutated one by making a functional protein that serves both viruses

Simultaneous infection –> Genome of virus A partially or completely coated in surface protein from virus B

Humoral and cell-mediated immunty
Reversion to virulence (rare)
“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)

Even though its a live attenuated vaccine, it can be given to HIV pts if they don’t show signs of immunodeficiency

Only humoral response
“SalK = Killed. RIP Always”
Rabies, Influenza (injected), Salk Polio, HAV

HBV (Ag = recombinant HBsAg) HPV (6, 11, 16, 18)

All DNA viruses except Parvoviridae

Parvoviridae (Parvovirus) “Part-of-a-virus” has less DNA”

Papilloma and Polyoma (circular supercoiled), and Hepadnaviruses (circular, incomplete)

All DNA viruses except for Papilloma, Polyoma, and Hepadnaviruses

All RNA viruses except for Reoviridae

Reoviridae “REpeatO virus is redundant with 2 strands”

“I went to a Retro Toga party where i drank Flavored Coronas and ate Hippy California Pickles”

Retrovirus, Togavirus, Flavivirus Corona virus, Hepevirus, Calicivirus, Picornavirus

Infectious: dsDNA viruses (except Poxvirus and HBV), and +ssRNA (like mRNA) viruses
Non-infectious: -ssRNA and dsRNA. Require polymerase contained in complete virion

All viruses are haploid except retrovirus which has 2 identical ssRNA molecules

All DNA viruses replicate in the nucleus except poxvirus
All RNA viruses replicate in the cytoplasm except influenza and retroviruses

“give PAP smears and CPR to Naked HEPpy”
DNA = PAPP, RNA = CRP and HEP
Papillomavirus, Adenovirus, Parvovirus, Polyomavirus, Calcivirus, Picornavirus, Reovirus, Hepevirus
Usually from cell membrane except for Herpes, which gets it from nuclear membrane

“HHAPPPPy”
Hepadna, Herpes, Adeno, Pox, Parvo, Papilloma, Polyoma

All except Pox (complex)

All except Pox (carries its own DNA dependent RNA pol)

dsDNA, Linear. Enveloped
HSV1, HSV2, VZV (HHV3), EBV (4), CMV (5), HHV6, HHV7, HHV8

dsDNA, partially circular. Enveloped
HBV: acute or chronic hepatitis
Vaccine available. Contains HBV surface Ag
Not a retrovirus but has a reverse transcriptase

dsDNA, Linear. Not enveloped

Febrile pharyngitis (sore throat, acute hemorrhagic cystitis), Pneumonia, Conjunctivitis (pink eye)

-ssDNA, Linear. Not enveloped
B19: aplastic crisis in sickle cell disease, Erythema infectionsum (5th disease, slapped cheek), RBC destruction in fetus --> hydrops fetalis and death, Pure RBC aplasia and RA-like symptoms in adults

dsDNA, Circular. Not enveloped

HPV 1,2,6,11: warts

Cervical intraepithelial neoplasia (CIN)

Cervical cancer (16, 18)

Vaccine for 16 and 18

dsDNA, Circular. Not enveloped
JC: progressive multifocal leukoencephalopathy (PML) in HIV pt
MBP present in CSF
BK: Transplant pt, commonly targets kidneys
"JC = Junky Cerebrum. BK = Bad Kidney"

dsDNA, Linear. Enveloped
Smallpox, Vaccina (cowpox - milkmaid's blisters)
Molluscum contagiosum: flesh colored dome lesions with central dimple

dsDNA, Linear. Enveloped
Oral (and some genital lesions), Gingivostomatitis, Keratoconjunctivitis, Temporal lobe encephalitis (most common cause of sporadic encephalitis in the US), Herpes Labialis
Latent in V ganglia
Respiratory secretions, Saliva

dsDNA, Linear. Enveloped
Genital (and some oral lesions), Herpes genitalis, Neonatal herpes
Latent in Sacral ganglia
Sexual contact, Perinatal

HHV3

dsDNA, Linear. Enveloped

Varicella-Zoster (chickenpox and shingles), Encephalitis, Pneumonia

Latent in DRG or Trigeminal Ganglia

Vaccine available

Respiratory secretions

HHV4

dsDNA, Linear. Enveloped

Infectious mononucleosis, Burkitt's Lymphoma, Hodgkin's Lymphoma, Nasopharyngeal carcinoma

Infects B cells

Latent in B cells

Respiratory secretions, Saliva

HHV5
dsDNA, Linear. Enveloped
Congenital infection, Mononucleosis (negative Monospot), Pneumonia, Retinitis
Immunosuppressed and Transplant pts
Owl's eye inclusions
Latent in mononuclear cells
Congenital, Transfusion, Sexual contact, Saliva, Urine, Transplant

dsDNA, Linear. Enveloped
Roseola (exanthem subitum): high fevers for several days that can cause seizures, followed by diffuse macular rash
Undetermined transmission
HHV7 a less common cause of Roseola

dsDNA, Linear. Enveloped
Kaposi sarcoma in HIV pt
Sexual contact

PCR is test of choice
Tzaneck test: smear of an open skin vesicle to detect multinucleated giant cells commonly seen in HSV1, HSV2, VZV
Infected cells also have intra-nuclear Cowdry A inclusions

EBV infecting B cells
Fever, HSM, Pharyngitis, and Lymphadenopathy (esp posterior cervical nodes)
15-20 years of age
Atypical lymphocytes seen on peripheral blood smear are not infected B cells, they are reactive Tc cells
+Monospot test

Heterophile Abs detected by agglutination of sheep or horse RBCs
Mononucleosis, Hodgkin's lymphoma, Endemic Burkitt's lymphoma, Nasopharyngeal carcinoma

dsRNA, Linear, Not enveloped, 10-12 segments
Icosahedral (double)
Coltivirus: Colorado tick fever. Arbovirus transmitted by arthropods (mosquitoes and ticks)
Rotavirus: #1 cause of fatal diarrhea in children

+ssRNA, Linear, Not enveloped, Non-segmented
Icosahedral
"PERCH"
Polio, Echovirus (aseptic meningitis), Rhinovirus (common cold), Coxsackievirus [aseptic meningitis, herpangina (mouth blisters, fever), hand-foot-and-mouth disease, myocarditis], HAV
All cause aseptic (viral) meningitis except rhinovirus and HAV
RNA is translated into 1 large polypeptide that is cleaved by proteases into functional viral proteins
All are enteroviruses (fecal-oral spread) except Rhinoviruses

+ssRNA, Linear, Not enveloped, Non-segmented
Icosahedral
HEV

+ssRNA, Linear, Not enveloped, Non-segmented
Icosahedral
Norovirus: viral gastroenteritis

+ssRNA, Linear, Enveloped, Non-segmented
Icosahedral
"CYD went from STL to the Nile"
HCV, Yellow fever, Dengue, St Louis encephalitis, West Nile Virus.
All except HCV are Arbovirus: transmitted by arthropods (mosquitoes and ticks)

+ssRNA, Linear, Enveloped, Non-segmented
Icosahedral
Rubella
Eastern/Western Equine Encephalitis (Arbovirus: transmitted by arthropods (mosquitoes and ticks))

+ssRNA, Linear, Enveloped
Icosahedral (HTLV), Complex and Conical (HIV)
Reverse transcriptase
HTLV: T cell leukemia, HIV: AIDS

+ssRNA, Linear, Enveloped, Non-segmented
Helical
Common cold and SARS

-ssRNA, Linear, Enveloped, 8 segments
Helical
Influenza virus

-ssRNA, Linear, Enveloped, Non-segments
Helical
Causes disease in children "PaRaMysovirus"
Parainfluenza (croup: seal-like barking cough), RSV (bronchiolitis in babies, treat with Ribavirin), Measles, Mumps
Surface F (fusion) protein causes respiratory epithelial cells to fuse and form multi-nucleated cells
Palivizumab (monoclonal Ab against F protein) prevents pneumonia caused by RSV infection in premature infants

-ssRNA, Linear, Enveloped, Non-segments
Helical
Rabies

-ssRNA, Linear, Enveloped, Non-segments
Helical
Ebola/Marburg hemorrhagic fever
Often fatal

-ssRNA, Circular, Enveloped, 2 segments

Helical

LCMV: Lymphocytic Choriomeningitis Virus

Lassa fever encephalitis

Spread by mice

-ssRNA, Circular, Enveloped, 3 segments
Helical
California encephalitis, Sandfly/Rift Valley fevers, Crimean-Congo hemorrhagic fever
Hantavirus (hemorrhagic fever, pneumonia)
All but Hantavirus are Arbovirus: transmitted by arthropods (mosquitoes and ticks)

-ssRNA, Circular, Enveloped, Non-segmented
Uncertain symmetry
HDV is a defective virus that requires HBV co-infection

Transcribe neg strand to +
Brings its own RNA-dependent RNApol
"Always Bring Polymerase Or Die Failing Replication"
Arenavirus, Bunyavirus, Paramyxovirus, Orthomyxovirus, Delta virus, Filoviruses, Rhabdoviruses

All are RNA viruses
"BOAR"
Bunyaviruses, Orthomyxoviruses (influenza), Arenaviruses, Reoviruses

Picornavirus
Causes common cold
Over 100 serologic types
Acid labile - destroyed by stomach acid

Flavivirus (also an arbovirus)
Aedes Mosquitoes
Monkey and human reservoir
High fever, black vomit, jaundice

Reovirus
"ROTAvirus = Right Out The Anus"
Infantile gastroenteritis: acute diarrhea
Winter, day-care centers, kindergartens
Villous destruction with atrophy leads to ↓ absorption of Na and loss of K
CDC recommends vaccination of all infants

Orthomyxoviruses
Hemagglutinin (promotes viral entry) and Neuraminidase (promotes progeny virion release)
Pts at risk for fatal bacterial superinfection
Rapid genetic changes
Killed vaccine is a major mode of protection. Vaccine containing live, temp sensitive mutant that replicates in the nose but not in lung also available for children

"Sudden Shifts more deadly than graDual Drift"
Shifts cause pandemics. Reassortment of viral genome; segments undergo high frequency recombination such as when human flu A virus recombines with swine flue A virus
Drift causes epidemics. Minor (antigenic drift) changes based on random mutation

Togovirus
Rubella (German 3 day measles): Fever, Postauricular adenopathy, Lymphadenopathy, Arthralgias, Fine Truncal rash that starts at head and moves down
Mild disease in children, Serious congenital disease (ToRCHS infection)

Paramyxovirus
"3Cs: Cough, Coryza, Conjunctivitis"
Koplik spots (red spots with blue-white center on buccal mucosa) and descending maculopapular rash. Presents last and spreads from head to toe including hands and feet (vs truncal rash in rubella)
SSPE (Subacute Sclerosing Panencephalitis) occuring years later, Encephalitis, Giant cell pneumonia (rarely in immunosuppressed)
Do not confuse with Roseola (HHV6)

Paramyxovirus
"Mumps makes your parotid glands and testes as big as POM-poms"
Parotitis, Orchitis (inflammation of testes), and aseptic Meningitis
Sterility (esp after puberty)

Rhabdoviruses. Bullet-shaped virus
Negri bodies in cytoplasm of neurons
Purkinje cells of cerebellum
Weeks to months incubation
Wound cleansing and vaccination +/- rabies immune globulin
Travels to CNS by migrating in a retrograde fashion up nerve axons
Fever, Malaise --> Agitation, Photophobia, Hydrophobia --> Paralysis, Coma --> Death
Bat, Raccoon, Skunk, Dog bites

Picornavirus (Non-enveloped +strand RNA)

Fecal-Oral

No carrier

Short incubation (weeks)

No risk of HCC

Asymptomatic

Acute

Hepadnavirus (Enveloped dsDNA)

Parenteral, Sexual, Vertical

Has Carriers

Long incubation (months)

Integrates into host genome and acts as oncogene

Flavivirus (Enveloped +sRNA)

Primarily blood, IVDU, Post-transfusion

Has Carriers

Long incubation

HCC risk from chronic inflammation

Chronic course

Cirrhosis, Carcinoma

RNA delta virus (enveloped, -ssRNA)

Parenteral, Sexual, Vertical

Has carriers

Superinfection - short. D infects after B

Co-infection - long. B and D infect together

HCC risk

Defective virus and dependent on HBV

Superinfection has worsened prognosis

Hepevirus (Non-enveloped +ssRNA)

Fecal-Oral especially with water-born epidemics

No carriers

Short intubation

No risk for HCC

High mortality rates in pregnant women

Enteric, Expectant, Epidemics

Fever, jaundice, elevated ALT/AST

B uses its own DNA dependent DNA pol to make full dsDNA

| Uses host RNA pol to make mRNA

IgM Ab to HAV

| Best test to detect HAV

IgG Ab indicates prior HAV infection and/or vaccination

| Protects against re-infection

Surface antigen indicates Hep B infection

Ab to HBsAg

| Indicates immunity to HepB

Antigen associated with core HBV

Ab to ABcAg
IgM = acute or recent infection
IgG = prior exposure or chronic infection
Positive during window period

A second, different antigenic determinant in the HBV core

| Indicates viral replication and therefore high transmissibility

Antibody to HBeAg

| Indicates low transmissibility

HBsAg +

Anti HBs -

HBeAg +

Anti HBe -

Anti HBc IgM

HBsAg -

Anti HBs -

HBeAg -

Anti HBe +

Anti HBc IgM

HBsAg +

Anti HBs -

HBeAg +

Anti HBe -

Anti HBc IgG

HBsAg +

Anti HBs -

HBeAg -

Anti HBe +

Anti HBc IgG

HBsAg -

Anti HBs +

HBeAg -

Anti HBe +

Anti HBc IgG

HBsAg -

Anti HBs +

HBeAg -

Anti HBe -

Anti HBc -

SECES

| HBsAg, HBeAg, AntiHBc, AntiHBe, AntiHBs

A,B,C,D,E

B, C, D

Interferons (alpha and pagylated)

| Lamivudine, Adefovir, Entecavir, telbivudine (Nucleoside Analogs --/ HBV DNApol)

+ssRNA, Linear, Enveloped. Diploid (2 molecules of RNA)
env: gp120 and gp41 formed from cleavage of gp160 to form envelope proteins
gp120 stuck on top of gp41 and attaches to host CD4 T cell. gp41 is transmembrane and mediates fusion and entry
gag (p24): caspid protein
pol: Reverse transcriptase, aspartate protease, integrase

ssRNA --> dsDNA --> integrates into host genome
Virus binds CCR5 (early) or CXCR4 (late) co-receptor and CD4 on T cell
Binds CCR5 and CD4 on macrophages
CCR5 homozygous mutation = immunity

Acquired through budding from host cell plasma membrane

RNA + reverse transcriptase --> caspid protein p24 --> Matrix protein p17 --> Lipid membrane --> gp41 goes through membrane and gp120 on top of it

Presumptive Dx made with ELISA for antiHIV Abs (sensitive with high false positive rule out with low threshold)

results are confirmed with Western blot assay for AntiHIV Abs (specific, high false negative rate, rule in with high threshold)

Falsely negative in first 1-2 months after infection

Falsely + in babies born to infected mothers (anti gp120 crosses placenta)

PCR/viral load determines amount of viral RNA in the plasma
High viral load associated with poor prognosis
Used to monitor effects of drug therapy

CD4+ less than 200 (normally 500-1500)

| HIV+ with AIDS-defining condition (PCP) or CD4/CD8 ratio less than 1.5

CD4 count drops then rebounds briefly (after HIV RNA copies peak) then steady decreases
HIV RNA copies peaks then drops (when CD4 count rebounds) then gradually rises

"4Fs"

Flu-like acute

Feeling fine (latent)

Falling count

Final crisis

Virus replicates in lymph nodes

Reactivation of past infections (TB, HSV, Shingles)
Disseminated bacterial and fungal infections
Non-Hodgkin's Lymphoma

Histoplasma capsulatum (causes only pulmonary symptoms in immunocompetent hosts)
Oval yeast cells w/in Macrophages
CD4 less than 100

C albicans (thrush)

Pseudohyphae

Oral if CD4 less than 400, Esophageal if CD4 less than 100

Bartonella henselae (bacillary angiomatosis

Biopsy reveals neutrophilic inflammation

Cryptosporidium

| Acid-fast cyst in stool when CD4 less than 200

JC virus reactivation (cause of PML)
Reactivation of latent virus
Results in demyelination
CD4 less than 200

Toxoplasma gondii
Many ring-enhancing lesions on imaging
CD4 below 100

Cryptococcus neoformans
India ink stain reveals yeast with narrow-based budding and large capsule
CD4 less than 50

CMV
Cotton wool spots on funduscopic exam
May also occur with esophagitis
CD4 less than 50

Directly associated with HIV. Must differentiate from other causes

HHV8 (causes Kaposi Sarcoma)
Do not confuse with bacillary angiomatosis caused by B henselae
Biopsy reveals lymphocytic inflammation

EBV

| Often found on lateral tongue

EBV

| Often on oropharynx (Waldeyer's ring)

HPV

| Anus (men who have sex with men) or Cervix (women)

EBV
Focal or multiple
Differentiate from toxoplasmosis

CMV

| Biopsy reveals cells with intra-nuclear (Owl's Eye) inclusion bodies

Aspergillus fumigatus

| Pleuritic chest pain, Hemoptysis, Infiltrates on imaging

Pneumocystis jirovecii

| CD4 less than 200

Mycobacterium avium-intracellulare

| CD4 less than 50

Conversion of a normal cellular protein (termed prion protein PrPc) to a β-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

Sporadic: Creutzfeldt-Jakob disease --> rapidly progressive dementia
Inherited: Gerstmann-Straussler-Scheinker Syndrome
Acquired: Kuru

Reovirus and All +ssRNA viruses except Coronavirus

All -ssRNA viruses + Coronavirus

"BAD"
All are -ssRNA viruses
Arenavirus, Bunyavirus, Delta virus