XIII - Virology Flashcards
Size of Viruses
20-300 nm
All viruses have a _____ coat.
protein coat (capsid), lipoprotein envelope in some
Virus capsids are composed of
repeating capsomeres
All helical viruses are
enveloped
Icosahedral (spherical) viruses can be enveloped or
naked
Viral Proteins
surface proteins, DNA or RNA polymerases, matrix protein, antigenic (serotypic) variants
Viral Proteins: Attachment to host cell receptors
surface protein
Viral Proteins: Interaction between nucleocapsid and envelope
matrix protein
Viral Proteins: Evasion of host defenses
antigenic (serotypic) variants
Lipid membrane derived from the host cell, acquired as the virus exits from the cell in a process called budding
viral envelope
All enveloped viruses acquire their envelope from plasma membrane except
herpesvirus - nuclear membrane
Enveloped viruses are _____ stable and _____ inactivated.
less stable, easily inactivated
Naked Viruses
RNA - Calici, Picorna, Reo, DNA - Parvo, Adeno, Papilloma, Polyoma
Purified nucleic acids of most dsDNA (except poxviruses and HBV) and (+) strand genome ssRNA viruses are
infectious
Naked nucleic acids of (-) strand ssRNA and dsDNA viruses are
not infectious
Naked nucleic acids of (-) strand ssRNA and dsDNA viruses require
enzymes contained in the complete virion
Infectious particles composed entirely of protein which case transmissible spongiform encephalopathies, highly resistant to inactivation, do not elicit an inflammatory response or an antibody response
Prions
Prion Proteins: Non-pathogenic
alpha-helix
Prions Proteins: Pathogenic
beta-pleated sheet
All viruses are haploid except
retroviruses
Genomes of RNA viruses can either have positive or negative
polarity
Some RNA viruses have a _____ genome.
segmented genome
Viruses with Segmented Genomes
Bunyavirus, Orthomyxovirus (influenza), Arenavirus, Reovirus
Must transcribe negative strand to positive, virion brings its own RNA-dependent polymerase
Negative-Strand RNA Viruses
Negative-Strand RNA Viruses
Arenavirus, Bunyavirus, Paramyxovirus, Orthomyxovirus, Filovirus, Rhabdovirus
Viral Genetics: Mutations can produce
antigenic, drug-resistant or attenuated variants
Viral Genetics: Causes epidemics
genomic reassortment
Viral Genetics: One virus produces a protein that can be used by another virus
complementation
Viral Genetics: Two different viruses infect the same cell
phenotypic mixing
Virus Life Cycle
attachment → penetration → uncoating → biosynthesis → maturation → release
Viral Growth Curve: A single virus particle infects a cell
Phase 0 - Entry
Viral Growth Curve: Virus decreases in number but continues to function
Phase 1 - Decline
Viral Growth Curve: No virus is detectable inside the cell
Phase 2 - Eclipse Period
Viral Growth Curve: Dramatic increase in amount of detectable viruses
Phase 3 - Rise Period
Viral Growth Curve: Amount of detectable viruses reach a plateau
Phase 4 - Latent Period
Viral Growth Curve: Marked derangement of cell function leading to lysis and cell death, remarkable amplification in number of viral particles
Phase 5 - Cytopathic Effect
Outcomes of Viral Infection: Visual or functional change in infected cells
Cytopathic Effect
Outcomes of Viral Infection: Oncogenic viruses induce transformation and unrestrained growth
Malignant Transformation
Outcomes of Viral Infection: Infected cells appear normal but are producing large numbers of progeny viruses
Commensal Symbiosis
Virulence Factors: Bind cytokines and block their ability to interact with receptors on their intended targets
Cytokine Decoys
Virulence Factors: Reduce the expression of antigen presenting cells and inactivate complement
Virokines
Viruses: Virulence Factors
antigenic variants of surface proteins, cytokine decoys, virokines
Persistent Viral Infections: Produce viruses for long periods of time, can serve as a source of infection for others
Carrier State
Persistent Viral Infections: Not producing virus at present but can be reactivated at a subsequent time
Latent Infections
Persistent Viral Infections: Long incubation period (years)
Slow Virus Infections
Viruses: Presumptive Identification
cytopathic effect, hemadsorption, interference, decrease in acid production (phenol red)
Presumptive Identification of Viruses: Attachment of RBCs to the surface of infected cells
hemadsorption
Presumptive Identification of Viruses: Disturbance with CPE by another virus
interference
Presumptive Identification of Viruses: Decrease in acid production by infected, dying cells
phenol red
Viruses: Definitive Diagnosis
complement fixation, hemagglutination inhibition, neutralization, fluorescent-antibody assay, radioimmunoassay, Enzyme-Linked Immunosorbent Assay (ELISA)
Virus Serologic Tests: Finding an antibody in one who previously had none
seroconversion
Virus Serologic Tests: Ig in current infection
IgM
Virus Serologic Tests: Ig that can be from previous infection
IgG
Gold Standard in Viral Dagnosis
viral DNA/RNA
Vaccines: Induce humoral and cell-mediated immunity but may revert to virulence on rare occasions, dangerous to give to immunocompromised patients or their close contacts
Live-Attenuated Vaccines
Only live-attenuated vaccine that may be given to HIV (+) patients
MMR
Live-Attenuated Vaccines
yellow fever, chicken pox (VZV), polio (Sabin’s), MMR
Vaccines: Induce only humoral immunity but are stable
Killed Vaccines
Killed Vaccines
rabies, influenza, polio (Salk’s), hepatitis A
Recombinant Vaccines
Hepatitis B (HBsAg), HPV (6, 11, 16, 18)
Hepatitis Virus: A
Picornaviridae
Hepatitis Virus: B
Hepadnaviridae
Hepatitis Virus: C
Flaviviridae
Hepatitis Virus: D
not classified
Hepatitis Virus: E
Caliciviridae
DNA Viruses
Hepadna, Herpes, Adeno, Pox, Parvo, Polyoma, Papilloma
All DNA viruses have dsDNA except
Parvovirus - ssDNA
All DNA viruses have linear DNA except
Papilloma, Polyoma, Hepadna
All DNA viruses are icosahedral except
Poxvirus - complex symmetry
All DNA viruses replicate in the nucleus except
Poxvirus - cytoplasm, Guarnieri bodies
Naked DNA Viruses
Parvovirus, Adenovirus, Human Papillomavirus
Naked DNA Viruses: Respiratory, transplacental, non-oncogenic, no vaccine
Parvovirus
Naked DNA Viruses: Respiratory, fecal-oral, non-oncogenic, vaccine available
Adenovirus
Naked DNA Viruses: Sexual, skin contact, oncogenic, vaccine available
Human Papillomavirus
Naked virus with icosahedral symmetry, ssDNA genome, one serotype
Parvovirus B19
Parvovirus: Transmission
respiratory droplets, transplacental
Parvovirus: Infections
Erythema Infectiosum (5th Disease), Aplastic Crisis, Fetal Infections, Arthritis, Chronic B19 Infection
Bright red cheeks (slapped cheeks), fever, coryza, sore throat
Erythema Infectiosum (5th Disease) - Parvovirus B19
Transient but severe aplastic anemia in children, sickle cell anemia, thalassemia, spherocytosis
Aplastic Crisis - Parvovirus B19
Parvovirus Fetal Infections: 1st Trimester
fetal death
Parvovirus Fetal Infections: 2nd Trimester
hydrops fetalis
Viral immune-complex arthritis of small joints
Parvovirus Arthritis
Chronic Parvovirus B19 infection causes _____ in immunodeficient patients.
pancytopenia
Naked virus, dsDNA, icosahedral nucleocapsid, only virus with fiber (penton), 41 antigenic types, Cowdry type B intranuclear inclusions
Adenovirus
Adenovirus: Transmission
aerosol droplet, fecal-oral, direct contact
Adenovirus: URT
pharyngitis, conjunctivitis, coryza
Adenovirus: LRT
bronchitis, atypical pneumonia
Adenovirus: GIT
acute gastroenteritis
Adenovirus: GUT
hemorrhagic cystitis
Adenovirus: Histopathology
Cowdry type B intranuclear inclusions
Naked virus with circular dsDNA, icosahedral nucleocapsid, at least 100 types
HPV
HPV: Transmission
sexually, direct contact
Infect squamous cells and induce formation of cytoplasmic vacuole (koilocytes), genes E6 & E7
HPV
HPV: Encode proteins that inactivate tumor suppressor genes
genes E6 & E7
HPV: Skin and plantar warts
HPV 1-4
HPV: Genital warts (condyloma acuminata), respiratory tract
HPV 6 & 11
Most common viral STD
HPV
HPV: Carcinoma of cervix, penis, anus
HPV 16, 18, 31, 33
HPV: Treatment for Genital Warts
Podophyllin
HPV: Treatment for Skin Warts
Liquid Nitrogen
HPV: Treatment for Plantar Warts
Salicylic Acid
HPV: Prevention
vaccine for HPV 6, 11, 16, 18, 9-26 y.o.
Only causes disease in immunocompromised hosts, causes progressive multifocal leukoencephalopathy (PML) in AIDS patients
JC Polyoma Virus
Demyelinating disease that affects oligodendrocytes characterized by deficits in speech, coordination and memory, AIDS patients
Progressive Multifocal Leukoencephalopathy (PML)
Only causes disease in immunocompromised hosts, causes hemorrhagic cystitis and nephropathy in patients with solid organ (kidney) and bone marrow transplants
BK Polyoma Virus
Enveloped DNA Virsues
HSV, VZV, EBV, CMV, HHV
Herpesviruses
CMV, HSV, EBV, VZV
Enveloped virus, icosahedral nucleocapsid, linear dsDNA, vesicle filled with virus particles and cell debris, multinucleated giant cells on Tzanck smear, large, pink-purple intranuclear inclusions (Cowdry type A)
Herpes Simplex Virus
Herpes Simplex Virus: Transmission
HSV 1 - saliva, direct (above umbilicus), HSV 2 - sexual, transvaginal (below umbilicus)
Herpes Simplex Virus: Site of Latency
HSV 1 - trigeminal ganglia, HSV 2 - lumbosacral ganglia
HSV: Gingivostomatitis, herpes labialis (lips), keratoconjunctivitis, temporal lobe encephalitis, herpetic whitlow (fingers), herpes gladiatorum (trunk)
HSV 1
HSV: Genital herpes (painful anogenital vesicles), neonatal herpes (contact within birth canal), aseptic meningitis
HSV 2
Herpes Simplex Virus: Treatment
Acyclovir
Needs virus kinase to be activated, analogue of guanine, shortens duration of lesions, reduces the extent of shedding of the virus, no effect on the latent sate
Acyclovir
Enveloped virus, icosahedral nucleocapsid, linear dsDNA, infects URT, hematogenous spread to the skin, becomes latent in the dorsal root ganglia, may reactivate as zoster, multinucleated giant cells with intranuclear inclusions
Varicella-Zoster Virus
Varicella-Zoster Virus: Transmission
respiratory droplets, direct contact with lesions
Varicella-Zoster Virus: Diseases
Varicella, Zoster, Ramsay Hunt Syndrome
VZV: Incubation period of 14-21 days, vesicular centrifugal rash in different stages (dewdrop on a rose petal), pneumonia, encephalitis, Reye’s Syndrome
Varicella
Aspirin in Pediatric Cases
Kawasaki, ARF, JRA
VZV: Painful vesicles along dermatomal distribution, debilitating pain (postherpetic neuralgia)
Zoster
VZV: Involvement of geniculate ganglion causes facial nerve paralysis
Ramsay Hunt Syndrome
Varicella-Zoster Virus: Site of Latency
dorsal root ganglia
Varicella-Zoster Virus: Treatment
Acyclovir - moderate to severe (shortens duration of lesions)
Enveloped virus, icosahedral nucleocapsid, linear dsDNA, cultured in shell tubes, (-) neutrophil test
Cytomegalovirus
Cytomegalovirus: Transmission
body fluids, transplacental, organ transplant
Immediate early proteins, giant cells with owl’s-eye nuclear inclusions
Cytomegalovirus
Cytomegalovirus: Translated from premade mRNAs, impair assembly of the MHC class I-viral peptide complexes
Immediate Early Proteins
Cytomegalovirus: Diseases
congenital CMV, heterophil (-) mononucleosis, systemic CMV
Most common cause of congenital abnormalities
Cytomegalovirus
Microcephaly, seizures, deafness, jaundice, purpura (blueberry muffin), most common when mother is infected in the 1st trimester
Congenital CMV
Fever, lethargy, abnormal lymphocytes in peripheral blood smears
Heterophil (-) Mononucleosis
Pneumonitis, hepatitis, colitis, retinitis in HIV
Systemic CMV
Cytomegalovirus: Treatment
Gancyclovir (resistant to Acyclovir), Foscarnet - retinitis
Enveloped virus, icosahedral nucleocapsid, linear dsDNA, infects mainly lymphoid cells (B-cells → Downey cells), elicits specific antibodies and nonspecific heterophil antibodies
Epstein-Barr Virus
Epstein-Barr Virus: Transmission
saliva
Kissing Disease
Epstein-Barr Virus
Epstein-Barr Virus: Diseases
Infectious Mononucleosis, malignancies
Fever, sore throat, lymphadenopathy, splenomegaly, splenic rupture
Infectious Mononucleosis
Epstein-Barr Virus: Malignancies
Burkitt’s Lymphoma (Africans), B-cell Lymphomas, Nasopharyngeal CA (Chinese), Hairy Leukoplakia (AIDS)
Malignancy of vascular endothelial cells, flat to nodular dark purple skin lesions at multiple sites
Kaposi’s Sarcoma (Human Herpesvirus 8)
Kaposi’s Sarcoma: Treatment
surgical excision, radiation
Only disease that has been eradicated from Earth
Smallpox (Variola Virus)
Largest virus, brick-shaped poxvirus, Guarnieri bodies (intracytoplasmic eosinophilic inclusions)
Smallpox (Variola Virus)
Smallpox: Transmission
aerosol, contact
Smallpox: Incubation Period
7-14 days
Smallpox: Findings
prodrome of fever and malaise followed by centrifugal rash
Pinkish, papular skin lesions with an umbilicated center, Henderson-Peterson bodies (intracytoplasmic eosinophilic inclusions)
Molluscum Contagiosum
Molluscum Contagiosum: Transmission
direct contact
Molluscum Contagiosum: Treatment
Cifodivir
Enveloped virus, incomplete circular dsDNA
Hepadnaviridae (Hepatitis B)
Hepatitis Types: Asymptomatic
Hepatitis A
Hepatitis Types: Blood-borne
Hepatitis B
Hepatitis Types: Chronic, cirrhosis, carcinoma, carriers
Hepatitis C
Hepatitis Types: Enteric, expectant mothers, epidemics
Hepatitis E
Hepatitis Types: Enteric infections
Hepatitis A & E
Hepadnaviridae: Transmission
blood, birth, sexual
Hepadnaviridae: Virulence Factors
HBsAg - surface antigen, HBcAg - core antigen, HBeAg - e antigen
Only DNA virus that produces DNA by reverse transcription with mRNA as template
Hepadnaviridae (Hepatitis B)
Hepadnaviridae causes hepatocellular injury due to
immune attack (HBV has no cytopathic effect)
Hepadnaviridae: Incubation Period
10-12 weeks
Fever, anorexia, jaundice, dark urine, pale feces, elevated transaminase levels, cirrhosis, hepatocellular CA, autoimmune vasculitides (polyarteritis nodosa)
Hepadnaviridae (Hepatitis B)
Hepatitis B Complications: Functional renal failure from hepatic injury in the abscence of renal pathology
Hepatorenal Syndrome
Hepatitis B Complications: Vascular dilatations cause overperfusion relative to ventilation leading to V/Q mismatch and hypoxemia
Hepatopulmonary Syndrome
Hepatitis B Complications
hepatorenal syndrome, hepatopulmonary syndrome, portal HPN, hepatic encephalopathy
Hepadnaviridae: Treatment
Interferon α, Lamivudine
Hepadnaviridae: Prevention
vaccination - first vaccine to prevent human cancer
All RNA viruses have ssRNA except
Reovirus, Rotavirus (dsRNA)
All RNA viruses replicate in the cytoplasm except
Influenza, Retrovirus (nucleus)
Picornaviridae
Polio, Echo, Rhino, Coxsackie, Hepatitis A
Naked nucleocapsid, ssRNA with (+) polarity, oral-fecal transmission, replicates in motor neurons in the anterior horn of the spinal cord causing paralysis
Poliovirus
Host range is limited to primates due to the binding of the viral capsid protein to a receptor found only on primate cell membranes
Poliovirus
Has 3 serologic (antigenic) types based on different antigenic determinants on the outer capsid proteins
Poliovirus
Poliovirus: Diseases
asymptomatic, abortive poliomyelitis, non-paralytic poliomyelitis, paralytic poliomyelitis
Poliovirus: Most common clinical form, mild, febrile illness, headache, sore throat, nausea, vomiting
abortive poliomyelitis
Poliovirus: Aseptic meningitis
non-paralytic poliomyelitis
Poliovirus: Flaccid paralysis, permanent motor nerve damage
paralytic poliomyelitis
Poliovirus: Histopathology
Cowdry type B intranuclear inclusions
Poliovirus: Prevention
killed vaccine (Salk, IPV), live-attenuated vaccine (Sabin, OPV)
Polio Vaccine: Interrupts transmission
live-attenuated vaccine (Sabin, OPV)
Polio Vaccine: Induces humoral IgG
killed vaccine (Salk, IPV), live-attenuated vaccine (Sabin, OPV)
Polio Vaccine: Induces intestinal IgA
live-attenuated vaccine (Sabin, OPV)
Polio Vaccine: Affords secondary protection by spread to others
live-attenuated vaccine (Sabin, OPV)
Polio Vaccine: Interferes with replication of virulent virus in gut
live-attenuated vaccine (Sabin, OPV)
Polio Vaccine: Reverts to virulence
live-attenuated vaccine (Sabin, OPV)
Polio Vaccine: Co-infection with enteroviruses may impair immunization
live-attenuated vaccine (Sabin, OPV)
Polio Vaccine: Can cause disease in the immunocompromised
live-attenuated vaccine (Sabin, OPV)
Polio Vaccine: Injection
killed vaccine (Salk, IPV)
Polio Vaccine: Oral
live-attenuated vaccine (Sabin, OPV)
Polio Vaccine: Requires refrigeration
live-attenuated vaccine (Sabin, OPV)
Polio Vaccine: Short immunity
killed vaccine (Salk, IPV)
Polio Vaccine: Long-lasting immunity
live-attenuated vaccine (Sabin, OPV)
Naked nucleocapsid, ssRNA, (+) polarity, classified based on pathogenicity in mice
Coxsackievirus
Coxsackievirus: Transmission
oral-fecal
Coxsackievirus A: Diseases
herpangina, hand-foot-and-mouth disease, hemorrhagic conjunctivitis, aseptic meningitis
Coxsackievirus B: Diseases
pleurodynia, myocarditis, pericarditis, aseptic meningitis
Coxsackievirus: Fever, sore throat, tender vesicles in oropharynx
herpangina
Coxsackievirus: Vesicular rash on hands and feet and ulcerations in the mouth
hand-foot-and-mouth disease
Coxsackievirus: Fever, severe pleuritic chest pain
pleurodynia
Coxsackievirus: Fever, chest pain, congestive failure
myocarditis, pericarditis
Most common cause of myocarditis and pericarditis
Coxsackievirus
Most common cause of aseptic meningitis
Coxsackievirus
Coxsackievirus, Poliovirus and Echovirus are
enteroviruses
Enteric Cytopathic Human Orphan
ECHOvirus
Virus initially not associated with any disease
Echovirus
Aseptic meningitis, URTI, febrile illness ± rash, infantile diarrhea, hemorrhagic conjunctivitis
Echovirus
Echovirus: Transmission
fecal-oral
Only respiratory picornavirus, causes common colds
Rhinovirus
Naked nucleocapsid virus, ssRNA, (+) polarity, more than 100 serotypes, affect mainly the nose and conjunctiva, replicates better at 33°C, acid-labile, host range limited to humans and chimpanzees
Rhinovirus
Rhinovirus: Transmission
aerosol droplets, hand-to-nose contact
Naked nucleocapsid virus, ssRNA, (+) polarity, frequently infects children, self-limited hepatitis, anti-HAV IgM (most important test), Enterovirus 72, has 1 serotype
Hepatitis A Virus (Picornaviridae)
Hepatitis A Virus: Transmission
fecal-oral
Hepatitis A Virus: Diagnosis
anti-HAV IgM
Fecal-oral transmission, no chronic carrier state, no cirrhosis, no hepatocellular CA, high mortality in pregnant women, causes hepatitis epidemics
Hepatitis E Virus (Caliciviridae)
Non-enveloped virus, icosahedral nucleocapsid, one piece of ssRNA, (+) polarity, sudden onset of vomiting and diarrhea accompanied by fever and abdominal cramping
Norwalk Virus/Norovirus (Viral Gastroenteritis)
Most common cause of non-bacterial diarrhea in adults
Norwalk Virus/Norovirus
Naked double-layered capsid with 10-11 segments of dsRNA, most common cause of childhood diarrhea
Rotavirus (Viral Gastroenteritis)
Enveloped virus, helical nucleocapsid, segmented ssRNA, (-) polarity, most common cause of respiratory tract infections
Influenza Virus
Influenza Virus: Major Antigens
hemagglutinin (H), neuraminidase (N)
Influenza Virus: Transmission
respiratory droplet
Influenza Virus: Worldwide epidemics (pandemics)
Influenza A
Influenza Virus: Major outbreaks
Influenza B
Influenza Virus: Mild respiratory tract infections, does not cause outbreaks
Influenza C
Influenza Virus: Pathogenesis
Envelope → 2 different types of spikes: hemagglutinin (H), neuraminidase (N)
Influenza Virus: 16 types of hemagglutinin (H), 9 types of neuraminidase (N)
Influenza A
Binds to the cell surface receptor (neuraminic acid/sialic acid) to initiate infection of the cell, target of neutralizing antibody
hemagglutinin
Cleaves neuraminic acid (sialic acid) to release progeny virus from infected cell, degrades the protective layer of mucus in the respiratory tract → enhances access to the respiratory epithelial cells
neuraminidase
Animal influenza viruses are the source of RNA segments that encode the antigenic _____ variants that cause epidemics among humas.
antigentic shift
Creation of new influenza variants
Reassortment
Common source of new influenza variants
aquatic birds (waterfowl)
Influenza “Mixing Bowl”
Pigs
Influenza Variants: Waterfowl
H1-H16, N1-N9
Influenza Variants: Humans
H1-H3, N1 and N2
Influenza: Only a human virus (no animal source), undergoes antigenic drift, new version every year
Influenza B
Influenza Variants: Major changes based on the reassortment of segments of the genome RNA, causes pandemics
antigenic SHIFT
Influenza Variants: Minor changes based on mutations in the genome RNA
antigenic DRIFT
Influenza: Incubation Period
24-48 hours
Fever, myalgias, headache, sore throat, cough
Influenza
Influenza: Complications
Staphylococcal Pneumonia, Reye’s Syndrome
Influenza: Treatment
Oseltamivir, Zanamivir, Influenza A - Amantadine, Rimantadine (Parkinson’s medicine, prevents viral uncoating)
Influenza: Prevention
annual vaccination
Paramyxoviridae
Parainfluenza, RSV, Measles, Mumps
Paramyxoviridae: Hemagglutinin (+), Neuraminidase (-), Fusion Protein (+)
Measles
Paramyxoviridae: Hemagglutinin (+), Neuraminidase (+), Fusion Protein (+)
Mumps, Parainfluenza
Paramyxoviridae: Hemagglutinin (-), Neuraminidase (-), Fusion Protein (+)
RSV
Enveloped virus, helical nucleocapsid, one piece of ssRNA, (-) polarity, infects URT, spreads to reticuloendothelial cells, hematologic spread to skin, transiently depress cell-mediated immunity
Measles
Multinucleated giant cells (Warthin-Finkeldey bodies) form as a result of the fusion protein in the spikes - characteristic of the lesions, lifelong immunity after recovery
Measles
Measles rash is caused by
cytotoxic T cells, attacking the infected vascular endothelial cells in the skin
Measles: Shortly after the rash appears, the virus can no longer be recovered and the patient _____ spread the virus.
can no longer spread the virus
Measles: Incubation Period
10-14 days
Measles: Pathognomonic Sign
Koplik’s Spots
Measles: Bright red lesions with white central dot on buccal mucosa
Koplik’s Spots
Measles: Rash
face → trunk → extremities → palms/soles
Rash: face → trunk → extremities → palms/soles
Measles
Measles: Complications
encephalitis, pneumonia, subacute sclerosing panencephalitis (SSPE) or Dawson disease
Measles: Triad
cough, coryza, conjunctivitis
Measles: Prevention
live-attenuated vaccine, Vitamin A - reduces severity
Enveloped virus, helical nucleocapsid, one piece of ssRNA, (-) polarity, initially infects URT, spreads to local lymph nodes, hematogenous spread to parotid glands, testes, ovaries, meninges, pancreas
Mumps
Mumps: Transmission
respiratory droplets
Mumps: Incubation Period
18-21 days
Tender swelling of the parotid glands (parotitis) with increased pain when drinking citrus juices, orchitis, meningitis, resolves in 1 week
Mumps
Mumps: Prevention
live-attenuated vaccine
Surface spikes are fusion proteins (not hemagglutinin or neuraminidase) which causes cells to fuse, forming multinucleated giant cells (syncitia), humans are the natural hosts
Respiratory Syncitial Virus
Most important cause of pneumonia and bronchiolitis in infants
Respiratory Syncitial Virus
Severe disease in infants due to immunologic cross-reaction with maternal antibodies
Respiratory Syncitial Virus
Respiratory Syncitial Virus: Treatment
Ribavirin
Inspiratory stridor, cough, hoarseness, steeple sign (subglottic stenosis)
Laryngotracheobronchitis / Croup (Parainfluenza Virus 1 & 2)
Laryngotracheobronchitis: Treatment
Racemic Epinephrine
Bullet-shaped enveloped virus with helical nucleocapsid, one piece of ssRNA, (-) polarity
Rabies
Rabies: Transmission
animal bite - dog, cats, skunks, racoons, bats
Multiplies locally at the bite site, infects sensory neurons and moves by axonal transport to CNS
Rabies
Rabies: Histopathology
Negri bodies
Rabies: Incubation Period
2-16 weeks - depends on bite site
Confusion, lethargy, hypersalivation, laryngospasm, hydrophobia, invariably fatal when encephalitis develops
Rabies
Rabies: Treatment and Prevetion
pre- and post-exposure vaccine (only vaccine routinely used post-exposure), post-exposure Ig
Rabies Post-Exposure Prophylaxis: Touching or feeding animals, licks on skin
Category I - no treatment
Rabies Post-Exposure Prophylaxis: Nibbling of uncovered skin, minor scratches or abrasions without bleeding, licks on broken skin
Category II - vaccine
Rabies Post-Exposure Prophylaxis: Single or multiple transdermal bites or scratches, contamination of mucous membranes with saliva from licks, exposure to bat bites or scratches
Category III - vaccine + Ig
Enveloped virus, helical nucleocapsid, one piece of ssRNA, (+) polarity, prominent club-shaped spikes forming a corona, 2 serotypes
Coronavirus
Coronavirus: Reservoir
horseshoe bat
Coronavirus: Intermediate Host
civet cat
Coronavirus: Transmission
respiratory droplets
Coronavirus: Diseases
common cold, Severe Acute Respiratory Syndrome (SARS)
SARS: Incubation Period
2-10 days
Atypical pneumonia rapidly progressing to ARDS, virus binds to ACE-2 receptors, non-cavitary “ground glass” infiltrates
Severe Acute Respiratory Syndrome (SARS)
Enveloped virus, icosahedral nucleocapsid, one piece of ssRNA, (+) polarity, flavivirus, 4 serotypes
Dengue
Dengue: Vector
Aedes aegypti mosquito
Dengue: Diagnosis
dengue IgM, tourniquet test
Influenza-like syndrome with maculopapular rash and severe pains in muscles and joints (breakbone fever), leukopenia, thrombocytosis, hemorrhagic shock due to cross-reacting antibody during 2nd infection
Dengue
Probable Dengue
endemic area, fever ± (nausea, vomiting, rash, aches/pains, tourniquet test (+), leukopenia, any warning sign)
Dengue: Warning Signs
abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleed, lethargy, restlessness, liver enlargement > 2cm, increase in Hct concurrent with rapid decrease in PC
Severe Dengue
severe plasma leakage (shock, fluid accumulation with respiratory distress), severe bleeding, severe organ involvement (AST or ALT ≥ 1000, impaired consciousness)
Dengue: Prevention
insecticides, draining stagnant water, mosquito repellant
Enveloped virus, one piece of ssRNA, (+) polarity, 6 serotypes, hypervariable region in envelope glycoprotein
Hepatitis C
Hepatitis C: Diagnosis
anti-HCV or HCV RNA
Most prevalent blood-borne pathogen
Hepatitis C
IV drug abusers, needle-stick injury, vertical transmission, sexual transmission
Hepatitis C
Most common needle-stick injury pathogen
Hepatitis B
Replication in liver enhanced by liver-specific micro-RNA, hepatocellular injury due to immune attack, alcoholism greatly enhances rate of hepatocellular CA, chronic carriage is higher than HBV
Hepatitis C
Hepatitis C: Incubation Period
8 weeks
Hepatitis C: Autoimmune Reactions
thyroiditis, autoantibodies, MPGN, porphyria cutanea tarda, DM
Main cause of essential mixed cryoglobulinemia
Hepatitis C
Hepatitis C: Treatment for Acute Disease
Interferon
Hepatitis C: Treatment for Chronic Disease
Peginterferon, Ribavarin
Hepatitis C: Treatment for Severe Disease
liver transplant
Most common indication for liver transplant
Hepatitis C
Enveloped virus, icosahedral nucleocapsid, one piece of ssRNA, (+) polarity, togavirus
Rubella
Rubella: Transmission
respiratory droplets, transplacental
Rubella: Diseases
German Measles, Congenital Rubella Syndrome
German Measles: Incubation period
14-21 days
Prodrome followed by 3-day maculopapular rash and posterior CLAD, rash (face → trunk → arms/legs), immune-complex polyarthritis in adults
German Measles (Rubella)
Infected during 1st trimester, PDA, congenital cataracts, sensorineural deafness, mental retardation
Congenital Rubella Syndrome
Rubella: Prevention
live-attenuated vaccine (should not be given to immunocompromised or pregnant patients)
RNA viruses with reverse transcriptase
Retroviridae
Converts ssRNA viral genome into viral dsDNA
reverse transcriptase
Enveloped virus with 2 copies (diploid) of a ssRNA, (+) polarity, most complex retrovirus, many serotypes
Human Immunodeficiency Virus (HIV)
HIV: Transmembrane protein (TM) which is linked to a surface protein (SU)
fusion protein (gp41)
HIV: Attachment protein
gp120
HIV: Cone-shaped, icosahedral core containing the major capsid protein
CA (p24) - diagnosis
HIV: Directs entry of dsDNA provirus into the nucleus and is later essential for the process of virus assembly
MA (p17)
HIV: RNA is tightly packed with basic protein in a nucleocapsid structure that differs in morphology among diffent retrovirus genera
NC (p7)
HIV Genes: p24, p7, p17
gag
HIV Genes: Nucleocapsid, Matrix
gag
HIV Genes: Reverse transcriptase, Protease, Integrase
pol
HIV Genes: gp120, gp41
env
HIV Proteins: gag
p24, p7, p17
HIV Proteins: nucleocapsid
p24, p7
HIV Proteins: matrix
p17
HIV Proteins: pol
reverse transcriptase, protease, integrase
HIV Proteins: Transcribes RNA genome into DNA
reverse transcriptase
HIV Proteins: Cleaves precursor polyeptides
protease
HIV Proteins: Integrates viral DNA into host cell DNA
integrase
HIV Proteins: env
gp120, gp41
HIV Proteins: Attachment to CD4 protein, antigenicity changes rapidly
gp120
HIV Proteins: Fusion with host cell
gp41
HIV: Group-specific antigen, core, not known to vary, antibodies against this do not neutralize infectivity but serve as important serologic markers of infection
p24
HIV: Interacts with the CD4 receptor, mutates rapidly because of lack of editing, many antigenic variants, V3 - most immunogenic region, antibody neutralizes infectivity
gp120
HIV: Mediates fusion of the viral envelope with the cell membrane
gp41
HIV Genes: Activation of transcription of viral genes
tat
HIV Genes: Transport of late mRNAs to cytoplasm
rev
HIV Genes: Decreases CD4 and class I MHC proteins
nef
HIV Genes: Enhances hypermutation
vif
HIV Genes: Transport in non-dividing cells
vpr
HIV Genes: Enhances virion release
vpu
HIV: Transmission
originally from chimpanzees, transfer of body fluids, transplacental, perinatal, needlestick, sexual contact
Preferentially infects and kills helper (CD4) T lymphocytes, loss of cell-mediated immunity, high probability of opportunistic infections, main immune response consists of cytotoxic (CD8) T-lymphocytes
HIV
HIV Phases: Acquired through sexual contact, blood, perinatally
Phase 0 - Infection
HIV Phases: Rapid viral replication but HIV test is (-)
Phase 1 - Window Period
HIV Phases: Peak of viral load, (+) HIV test, mild flu-like illness lasting 1-2 weeks
Phase 2 - Seroconversion
HIV Phases: Asymptomatic, CD4 goes down, lasts 1-15 years
Phase 3 - Latent Period
HIV Phases: CD4 500-200, lasts 5 years, mild mucocutaneous, dermatologic and hematologic illness
Phase 4 - Early Symptomatic
HIV Phases: CD4 < 200, lasts 2 years, AIDS-defining illnesses develop
Phase 5 - AIDS
AIDS-Defining Illnesses: CD4 < 500
M. tuberculosis (disseminated TB), HSV (eophagitis), C. albicans (esophageal candidiasis), HHV-8 (Kaposi’s sarcoma)
AIDS-Defining Illnesses: CD4 < 200
P. jiroveci (PCP pneumonia), T. gondii (cerebral toxoplasmosis), C. neoformans (meningoencephalitis), C. immitis (coccidioidomycosis), C. parvum (chronic diarrhea)
AIDS-Defining Illnesses: CD4 < 50
M. avium (invasive pulmonary disease), H. capsulatum (histoplasmosis), CMV (retinitis)
Most common AIDS-defining illnesses
P. carinii pneumonia (PCP), esophageal candidiasis, wasting, Kaposi’s sarcoma, disseminated MAC
Most common among AIDS-defining illnesses
P. carinii pneumonia (PCP)
HIV: Presumptive Diagnosis
ELISA
HIV: Definitive Diagnosis
Western Blot (gp41, p24)
HIV: Treatment
Highly Active Antiretroviral Therapy (HAART)
2 nucleoside inhibitors (Zidovudine, Lamivudine) and protease inhibitor (Indinavir), immune reconstitution syndrome in patients co-infected with HBV, HCV, MAC/MAI
Highly Active Antiretroviral Therapy (HAART)
HIV: General Prevention
condoms, not sharing needles, proper blood disposal, post-exposure prophylaxis
HIV: Perinatal Prevention
perinatal prophylaxis, CS delivery, breastfeeding cessation
Retrovirus causing adult T-cell leukemia and a HTLV-associated myelopathy, malignant T-calls with flower-shaped nucleus
Human T-cell Lymphotropic Virus (HTLV)
Thread-like virus, longest virus, outbreak of hemorrhagic fever in Zaire (1976), 100% mortality rate
Ebola Hemorrhagic Fever
Flavivirus, bird-mosquito-man cycle, initial self-limited febrile illness with progression to neuroinvasive disease
West Nile Fever
Flavivirus, most common cause of epidemic encephalitis, most prevalent in SEA, transmitted by Culex mosquitoes, thalamic infarcts on CT scan
Japanese B Encephalitis
