Week 12 Flashcards
Naked viruses
Naked viruses: nucleocapsid = [genome + capsid]
Enveloped viruses
How are they inactivated?
- Enveloped viruses: nucleocapsid + matrix/tegument + lipid bilayer + glycoprotein spikes
- Enveloped viruses can be inactivated via drying, detergents, pH, temperature
- This is because the lipid bilayer is required for infection of cells
- Enveloped viruses can be inactivated via drying, detergents, pH, temperature
DNA Virus Genome Types (5)
- Duplex, open ends: adenovirus and herpesvirus (open = say AH)
- Duplex, closed ends: poxvirus
- Duplex, closed circle: polyomarvirus and papillomavirus
- Duplex, inner strand incomplete: hepadnavirus
- Single stranded, linear: parvovirus
RNA Virus Genome Types (2)
- Coding strand = positive strand (same polarity as mRNA and functions as mRNA)
- Template strand = negative strand (opposite polarity of mRNA)
Capsid structures Types
- Capsid structures (protomer → capsomer → capsid)
- Icosohedral – rigid structure comprised that limits size of enclosed nucleic acid
- Helical – flexible structure that can accommodate any length of nucleic acid
Matrix/tegument
Proteinaceous layer – layer between capsid and envelope containing endogenous proteins/enzymes for viral assembly and initiating new infection
Envelope components
- Lipid bilayer derived from host cell membrane
- Glycoprotein spikes
DNA Virus
Capsid Structure?
Naked or Enveloped?
(NAME EXCEPTIONS TOO)
- DNA Viruses
- Capsid: icosahedral
- Exceptions: Pox
- Envelope: none
- Exceptions: Hepatitis B., Herpes viruses, and Pox
- Capsid: icosahedral
RNA Virus
Capsid Structure?
Naked or Enveloped?
(NAME EXCEPTIONS TOO)
- Capsid: icosahedral or helical
- Envelope
- Icosahedral: all naked
- Exceptions: Togaviruses and Flaviviruses
- Helical: all enveloped
- Exceptions: none
- Icosahedral: all naked
- Retroviruses have complex capsid and are enveloped
What are the general steps of virus life cycle?
- Virus Attachment Protein (VAP) binds to non-suspecting receptor on host PM
- Capsomere on naked virus
- Glycoprotein spike on envelope virus
- Virus penetration: release of nucleocapsid is dependent on pH changes → conformational change
- Endocytosis
- Fusion
- Uncoating of genome: release of genome from capsid
- Cellular Sites of Replication
Cellular Sites of Replication
RNA vs. DNA
(EXCEPTIONS?)
- RNA viruses: occurs in cytoplasm
- Exceptions: influenza and retroviruses (only virus to have 2 exact copies of its genome)
- DNA viruses: occurs in nucleus
- Exceptions: Pox and Hepatitis B
GENOME REPLICATION
RNA+ vs. RNA -
- Genome Replication: RNA-dependent RNA polymerase functions as replicase and transcriptase
- Positive Strand Virus: positive strand codes for mRNA to make proteins, one of which is an RNA poly → positive strand acts as template to make negative strand → negative strand serves as template for mRNA and positive genome production
- Negative Strand Virus: negative strand acts as template to make positive strand → positive strand serves as mRNA and as template for negative genome production
- Comes with RNA-dependent RNA polymerase in the virion
Protein production in DNA viruses
Three regulatory classes?
- Immediate-Early: regulatory proteins
- Early: genome replication
- Late: structural proteins
Provide examples of how viruses alter cell functions and appearance, intracellular defenses, and viral countermeasures.
- Evelopment: budding process of enveloped viruses to exit infected cells
- Cytopathology: host cell may be destroyed in process of evelopment
- Intracellular defenses: cells release interferon to activate immune response against infected cell
- Viral countermeasures: interrupt interferon signaling or encode anti-apoptotic proteins
Permissive vs. Non-permissive
- Permissive cells: allow for complete viral life cycle including release of virus
- Non-permissive cells: do not allow the viral life cycle to complete
Virus-Cell Interactions (5 TYPES)
- Lytic infection – virus production with cell death
- Abortive infection – infection of non-permissive cells with no infectious virus production
- Persistent infection – long-term virus-cell association with cell survival
- Chronic: virus replicates
- Latent: no replication but some viral gene expression
- Recurrent infection: has latent and lytic periods
- Transformation: oncogenic conversion caused directly by viral gene activities
Tropism
Tropism – a particular disease may be caused by several viruses that have a common tissue preference
Virulence factors
Virulence factors – required for pathogenicity and/or survival in the host; may not include factors required for viral growth
Attenuation
Attenuation – loss of virulence factors
Explain the differences between local and systemic viral infections with respect to replication sites, target organs, and disease manifestations.
- Local infection – virus replication at site of entry and spreads to adjacent cells
- Systemic infection
- Entry into host → primary replication → primary viremia → secondary replication → secondary viremia → disease → shedding (transmission to new host/cell)
- Primary is low viral load
- Secondary is high viral load
What if primary site of infection is target site of virus?
- If primary site of infection is target site of virus, disease is shorter incubation
- If secondary site is target tissue, disease is longer incubation
Viral modes of transmission
- Self-inoculation
- Inhalation
- Breaks in skin or mucoepithelial membranes
Sites of Entry (6)
Defense Mechanisms?
- Oropharynx – viruses can enter via aerosols or saliva
- Defense mechanism: mucous
- Respiratory tract – viruses can enter via inhalation
- Defense mechanism: temperature and mucociliary transport system
- Upper RT: 32 degrees Celsius gives rise to common cold
- Lower RT: 37 degrees Celsius gives rise to adenovirus
- Defense mechanism: temperature and mucociliary transport system
- GI tract – viruses can enter through our food and drink
- Defense mechanism: bile salts degrade enveloped viruses
- Skin – viruses can enter through trauma
- Conjuctiva – viruses enters via direct inoculation
- Defense mechanism: tears
- Genitourinary Tract: viruses enter via sex
- Defense mechanism: mucous, pH, urine
How do viruses causes damage?
- Cell killing by virus replication – budding can cause cell lysis
- Oncogenesis – can convert cells into tumor cells
- Immunopathology – activation of immune system to cause disease symptoms
Provide examples of viral counter-measures against host defenses.
- Cross BBB (ABs cannot reach this area)
- Pass beneath tight junction (restrict access of immune response)
- Viruses make IL-10 homologue (immunosuppression)
NAME EACH TYPE




Describe different types of exposure to viruses and provide examples of viruses that are transmitted in each situation.
- Crowded living conditions – rhinoviruses, influenza
- Certain occupations – HBV, HCV, HIV, HPV
- Lifestyle – HIV, HPV, herpesvirus
- Daycare centers – measles, mumps, rubella, rhinoviruses, influenza, herpesvirus
- Travel – arboviruses, respiratory viruses
Explain how viruses commonly found in healthy individuals and animals can cause disease in humans.
Normal Flora
Normal Flora
Sites and Examples
Normal Flora
- Oropharynx and Mouth
- Adenoviruses and cytomegalovirus (CMV)
- Large Intestines
- Adenoviruses and enterovirus
- Urinary/Reproductive Systems
- Papillomaviruses
Explain how each of the following affects susceptibility and severity of viral disease: age, immune status, general health, geography, and time of the year.
- Age
- Children – susceptible because immunologically naïve and small size/physiologic requirements
- Elderly – susceptible to new viral infections and reactivation due to decline in immune response
- Immune status – immunosuppressed individuals are at risk
- General health – poor nutrition leads to compromised immune system
- Geography – population density can spread disease
- Time of year – individuals spend more time inside during winter so higher concentration of air droplets
Explain the differences between outbreak, epidemic, and pandemic.
- Outbreak – introduction of a virus into a new area with immunologically naïve population
- Epidemic – spread of virus to larger geographic region
- Pandemic – worldwide spread of virus
Define:
Saprophytic, Symbiotic, Parasite, Pathogen
- Saprophytic – feeds on dead or decaying matter
- Symbiotic – mutually beneficial relationship with host
- Parasite – lives on or in a host solely to benefit itself
- Pathogen – when the parasite harms its host, it is called this
How fungi differ from bacteria?
- Fungi are eukaryotic
- Major sterol in cell membrane of fungi is ergosterol
Characteristics of Yeast
- Yeast
- Unicellular
- Mechanisms of division
- Nuclear fission
- Budding (blastoconidia or blastospores)
- Germ tube (pseudohyphae – only occurs with Candida albicans)
Characteristics of Molds
- Molds
- Multicellular
- Hyphae – tubular structures of cells
- Septated – partitioned
- Nonseptated – not-partitioned
- Mycelium – a mass of hyphae growing (like mold on bread)
- Conidia/spores – break off of hyphae at septum
Characterisitics of Dimorphic
- Dimorphic
- A mold in environment at 25 degrees Celsius and a yeast in humans at 37 degrees Celsius
Fungi Cellular Structure?
- Capsule – polysaccharide coating present on only some fungi (Cryptococcus neoformans)
- Cell wall – made up of:
- Mannoprotein
- Beta glucans
- Chitin
- Cell membrane
- Lipid bilayer with ergosterol
List some noninfectious medical problems from fungi.
- Allergies – hypersensitivity to fungi
- Mycotoxins
- Aflatoxins – Aspergillus flavus in grain storage
- Amatoxins/phallotoxins – poisonous mushrooms produce alpha-amanitin, which inhibits RNA Pol II (mRNA)
Diagnosostic Test used for Fungi?
- Diagnosis: KOH Prep
- Positive test indicates a cutaneous/mucosal fungal infection
Superficial Mycoses
Characterisitics and Examples (4)
Only 1 for SPM exam, 4 total otherwise.
- Characteristics
- Involves outer keratinized layer and noninvasive
- Tinea versicolor (caused by Malassezia fufur)
- Causes hypo/hyper pigmentated lesions
- Lipophilic and can infect intravenously through IVs
- NOT REQUIRED FOR SPM EXAM
- Tinea nigra – caused by Hortaea werneckii and causes lesions
- Black piedra – caused by Piedraia hortae and causes dark nodules on hair shafts
- White piedra – caused by Trichosporon genus and causes white growths around hair of groin
Cutaneous Mycoses
Characterisitics and Examples (5)
- Characteristics
- Involves keratinized layer → inflammation of epidermis and upper dermis
- Referred to as tinea and named by location on body (not an organism!)
- Caused by molds called Dermatophytes
- Itchy, flakey, red lesions
- Referred to as ringworm
-
tinea pedis – foot (athlete’s foot)
- Provides portal of entry for Group A Beta Strep (cellulitis)
- tinea cruris – groin (jock itch)
- tinea corporis – general body (classic Ringworm)
- tinua capitis – scalp
- tinea unguium – nails (called onychomycosis)
Subcutaneous Mycoses
Characterisitics and Examples (3)?
- Characteristics
- Infection of dermis and subcutaneous tissue
- Develops at site of trauma (i.e. rosebush thorn prick)
-
Sporotrichosis (Rose gardener’s disease)
- Caused by Sporothrix schenckii (dimorphic)
- Presents as lymphocutaneous nodules/legions following site of trauma up lymph
- Similar presentation caused by Mycobacterium marinum (from fish tanks)
-
Chromoblastomycosis
- Due to various pigmented molds
- Presents as slow growing cauliflower-like nodules
- Eumycotic mycetoma – seen in tropics (swelling)
Explain the concept of opportunistic infections.
Disruption of the normal delicate balance of various factors permits colonization, infection, and disease of opportunistic infections.
Describe epidemiology of and clinical syndromes from (3 total syndromes)
Candida (i.e. C. albicans, C. glabrata, C. krusei)
- Yeast or mold or dimorphic?
-
(YEAST)
- Part of normal flora
- Pathogenicity occurs endogenously
- Syndromes
- Mucosal: thrush – cottage cheese-like coating of mouth
- Cutaneous: intertrigo – red rash in between skin folds
- Candidemia: retinitis – fungus in bloodstream seeds in retina (via IV)
- IMPORTANT: positive respiratory samples never indicate pneumonia
Describe epidemiology of and clinical syndromes from…
Cryptococcus (i.e. C. neoformans)
- yeast or mold or dimorphic?
-
(YEAST)
- Prominent capsule that is identified with India Ink
- Strictly opportunistic pathogen seen predominately in AIDS
- Bird feces → lungs → brain
- Syndromes
- Cryptococcal Meningitis
Describe epidemiology of and clinical syndromes from…
Pneumocystis (fungi but treated as a protozoan)
Lacks ergosterol and does not respond to anti-fungals
Strictly opportunistic pathogen seen predominately in AIDS
Describe epidemiology of and clinical syndromes from…
Histoplasmosis
- Mold or yeast or dimorphic
-
Endemic Mycoses - DIMORPHIC
- Epidemiology: Ohio and Mississippi River valleys
- Transmission: mold grows in soil → infects macrophages → grows as yeast in human
- Patients not contagious in yeast form
- Symptoms: infects lungs
- Diagnosis: histology showing macrophages with many small intracellular yeast
Describe epidemiology of and clinical syndromes from…
Blastomycosis
- yeast or mold or dimorphic?
-
Endemic Mycoses - DIMORPHIC
- Epidemiology: Ohio and Mississippi River valleys
- Transmission: mold grows in soil → grows as yeast in human
- Patients not contagious in yeast form
- Symptoms: infects lungs/cutaneous lesions
- Diagnosis: histology showing broad-based budding during division
Describe epidemiology of and clinical syndromes from…
Coccidioidomycosis
- yeast or mold or dimorphic?
-
Endemic Mycoses - DIMORPHIC
- Epidemiology: arid Southwestern States (AZ and CA)
- Transmission: mold grows in soil → inhalation of spores → yeast grows in lungs
- Symptoms: asymptomatic but disseminated disease is lethal (skin/lung)
- Diagnosis: large spherules containing endospores
Describe epidemiology of and clinical syndromes from…
Aspergillus - most commonly Aspergillus fumigatus (or Aspergillus-like: Pseudallescheria boydii, Fusarium, Penicllium)
- mold or yeast or dimorphic?
- 3 total syndromes?
-
Invasive Molds
- Septated hyphae with 45 degree branching
- Neutropenia is biggest risk
- Clinical Syndromes
-
Allergic bronchopulmonary aspergillosis (ABPA) – colonization of airways leads to asthmatic symptoms
- Responds to steroids
-
Invasive aspergillosis (IA) – prolonged neutropenia and causes infarcts
- Responds to antifungals
-
Aspergilloma (or fungus ball) – in pre-existing lung cavity
- Responds to surgery
-
Allergic bronchopulmonary aspergillosis (ABPA) – colonization of airways leads to asthmatic symptoms
Describe epidemiology of and clinical syndromes from…
Mucormycosis – most commonly caused by Mucor (or Zygomyces)
- mold or yeast or dimorphic?
-
Invasive Molds
- Risk factors: DKA, steroids, neutropenia, iron overload
- Diagnosis: non-septated hyphae with 90 degree branching
- Clinical Syndromes
- Rhinocerebral: black necrotic eschars in nasal passage
Non-invasive Molds
Dermatophytes (see above)
Trichophyton, Microsporum
Flu-like symptoms (fever, coughing, chills, myalgia)
Influenza
Cold sores/blisters on the genitals or mouth
Herpes Simplex virus
Chicken pox: red sores all over the skin
Shingles: painful rash on half the body (neural)
- Varicella-zoster virus
- Varicella – Chicken pox: red sores all over the skin
- Zoster – Shingles: painful rash on half the body (neural)
- Oral hairy leukoplakia in AIDs
- White rash on edge of the tongue
Epstein-Barr Virus
Retinitis – inflammation of the eye
Cytomegalovirus
- Family:RNA Viruses
- Target:Influenza A
- MOA:M2 inhibitors
- Clinical:Not used clinically
Amantadine/Rimantadine
- Family: RNA Viruses
- Target: Influenza A & B
- MOA: Neuraminidase Inhibitor – prevents cleavage of HA and sialic acid à blocking release of virus
- Clinical:
- Zanamivir – powder (contraindicated in asthma pts)
- Oseltamivir – oral
Zanamivir/Oseltamivir(Tamiflu)
- Family: DNA Viruses
- Target: HSV, VZV
- (EBV – oral hairy leukoplakia in AIDs)
- MOA:
- DNA homolog: Acts as a DNA chain terminator
- Prodrug → active drug via viral thymidine kinase (TK)
- Clinical:
- Resistance via TK mutations
- Drug of choice for HSV encephalitis
Acyclovir (IV)
- Family: DNA Viruses
- Target: HSV, VZV
- MOA:
- Prodrug of Acyclovir that are activated in intestinal wall or liver
- More bioavailable form of Acyclovir
- Clinical:
- More Bioavailable than acyclovir in oral form
- Used for herpes labialis before symptom appear
Valacyclovir/Famciclovir (PO)
- Family: DNA Viruses
- Target: CMV
- MOA:
- Triphosphate that inhibits viral DNA synthesis
- Clinical:
- IV for therapeutics
- PO for prophylaxis
- CMV retinitis
- Very toxic (bone marrow)
Ganciclovir (IV) /Valganciclovir (po)
- Family: DNA Viruses
- Target: Resistant CMV, HSV, VZV
- MOA:
- Pyrophosphate analog that inhibits viral DNA synthesis
- Clinical:
- CMV retinitis
- Very toxic (kidney)
Foscarnet (IV)
- Family: Polyenes
- Target: Cell membrane
- MOA:
- Lipophilic molecule that binds to ergosterol
- Use:
- Candida, Cryptococcal,
- Mucormycosis (drug of choice)
- EXCEPT: Pseudallescheria
- Clinical:
- Tx: Meningitis, Neutropenia
- HIGH nephrotoxicity
- Less toxic versions available (Lipid versions)
Amphotercin (IV)
- Family: misc.
- Target: n/a
- MOA:
- interferes with nucleic acid synthesis
- Use:
- Candida, Cryptococcal,
- Clinical:
- In meningitis: used with amphotericin initially → fluconazole
- Toxic to bone marrow
Flucytosine (PO)
- Family: Azole
- Target: Cell membrane
- MOA:
- inhibits ergosterol synthesis
- Use:
- Candida albicans, Cryptococcal
- NOT MOLDS
- Clinical:
- Candida krusei & glabrata are resistant
- Tx: esophagitis, candidemia
Fluconazole
- Family: Azole
- Target: Cell membrane
- MOA:
- inhibits ergosterol synthesis
- Use:
- Sporotrichosis
- Histo & Blasto
- Clinical:
- Pulse therapy for onychomycosis
Intraconazole
- Family: Azole
- Target: Cell membrane
- MOA:
- inhibits ergosterol synthesis
- Use:
- Aspergillus (drug of choice)
- Clinical:
- Visual disturbances
Voriconazole
- Family: Azole
- Target: Cell membrane
- MOA:
- inhibits ergosterol synthesis
- Use:
- Mucormycosis (not used clinically)
- Clinical:
- Prophylaxis
Posaconazole
- Family: Azole
- Target: Cell membrane
- MOA:
- inhibits ergosterol synthesis
- Use:
- Aspergillus & Mucormycosis
- Clinical:
- New drug: expanding role
Isavuconazole
- Family: Echinocandins
- Target: Cell wall
- MOA:
- Inhibits synthesis of 1,3-beta-D glucan
- Use:
- Candida and Aspergillus
- Clinical:
- Tx: esophagitis, candidemia
Last line of defense against Aspergillus
Caspofungin (IV)
Can you mix 2 or 3 antifungals?
Mix 2 or 3 of these Antifungals → Extra toxicity and possible antagonism of MOAs
What are Newer Respitory Viruses? (5)
- Hantavirus Pulmonary Syndrome – noncardiogenic pulmonary edema due to inhalation of aerosolized saliva
- Metapneumovirus – upper and lower respiratory infections caused by paramyxovirus
- SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome) – caused by coronviruses
- Avian Influenza (Bird Flu) – very rare human-to-human transmission caused by Influenza A (H5N1 and H7N9)
- Can become pandemic once gain human virulence factors
- H1N1 (Swine Flu) – pandemic that is now in seasonal vaccine
Disease: Common Cold
Presentation, Etiology, Treatment?
Presentation: Coryza (runny nose)
Etiology: Rhinovirus or coronavirus
Treatment: Let run natural course
Disease: Sinusitis / Otitis Media / Mastoiditis
Presentation, Etiology, Treatment?
Presentation: Inflammation of ear drum, sinuses
Etiology: Assumed to be bacterial: Strep pneumonia, H. flu, or Moraxella catarrhalis
Treatment: Amoxicillin
Disease: Pharyngitis / Tonsillitis / Laryngitis
Presentation, Etiology, Treatment?
Presentation: Inflammation of pharynx, tonsils, larynx
Etiology: Viral, usually part of common cold or flu
Treatment: Make sure it’s not bacterial
Disease: Epiglottitis (Supraglottitis)
Presentation, Etiology, Treatment?
Presentation: In children: cellulitis of supraglottic region (vocal cords); fever; sore throat; drooling
Etiology: Haemophilus influenzae type b
Treatment: Beta-lactamase resistant antibiotic (Cefatriaxone)
Disease: Laryngotracheobronchitis (Croup)
Presentation, Etiology, Treatment?
Presentation: In children: inflammation of subglottic region (below vocal cords); barking cough; stridor; hoarseness
Etiology: Parainfluenza virus
Treatment: n/a
Disease: Tracheobronchitis / Bronchitis
Presentation, Etiology, Treatment?
Presentation: Cough
Etiology: Virus
Treatment: Make sure it’s not pneumonia
Disease: Whooping Cough (Pertussis)
Presentation, Etiology, Treatment?
Presentation: 1- to 3-week incubation; dry short coughs followed by inspiratory gasp or “whoop”; lymphocytosis
Etiology: Bordetella pertussis
Treatment: Macrolides (Azithromycin)
Disease: Bronchiolitis
Presentation, Etiology, Treatment?
Presentation: Occurs in first two years of life; wheezing; hyperaeration of lungs (air trapping)
Etiology: Respiratory Syncytial Virus (RSV), especially during winter
Treatment: Let run natural course
Disease: HAP
Presentation, Etiology, Treatment?
Presentation: Fever; cough; sputum; X-ray consolidation
Etiology: Pseudomonas (nosocomial)
Treatment: Sputum sent for Gram stain and culture
Disease: CAP
Presentation, Etiology, Treatment?
Presentation: Fever; cough; sputum; X-ray consolidation
Etiology:
- Normal anaerobes from aspiration
- Typical: Strep pneumoniae
- Atypical: Mycoplasma pneumoniae, Legionella pneumophila, Chlamydophila pneumoniae
Treatment: Sputum sent for Gram stain and culture
Disease: Post-influenza Pneumonia
Presentation, Etiology, Treatment?
Presentation: Fever; cough; sputum; X-ray consolidation
Etiology: Staph aureus
Treatment: Sputum sent for Gram stain and culture