Module 7 Flashcards

Viruses

Obligate intracellular pathogens that require host cells to complete life cycle

Features of viruses

1. Not made of cells

2. cannot reproduce independently

3. does not undergo self-division

Composition of viruses

Composed of just protein and nucleic acid genome

Describe the nucleic acid genome of viruses

Can be either DNA or RNA

• surrounded by protective protein coat = CAPSID

• some viruses contain lipid membrane envelope with glycoproteins for attachment

Life cycle of a virus

1. Attachment to the cell and entry

2. Production of new viral proteins

3. Replication of Virus genome within cell

4. Assembly and exit of new virus particles to go find another cell

Common routes of entry for viruses

• skin

• conjunctiva

• respiratory

• GI

• genitourinary

Tropism

the specificity of a virus for a particular host tissue or cell type

Types of Virus transmission

1. Contact transmission

2. Transmission between humans

3. Transmission from animals

Contact transmission

transmission via:

• aerosols/mucous

• fecal-oral

• skin lesions

• body fluids

Transmission between humans

• horizontal transmission from person to person (contact transmission)

• vertical transmission from mother to baby (placental, utero, breast milk)

Transmission from animals

Involves:

• vectors (birds, insects)

• vertebrate reservoirs (dogs and rabies)

3 main ways of viruses spreading within a host

1. Localized infection

2. Disseminated infection

3. Systemic infection

Localized infection

occurs at site of entry

viruses replicate in specific region of body

Disseminated infections

virus begins at primary site of infection and extends beyond to other regions of the body

Systemic infection

involves the spread of viruses throughout the body affecting multiple organs and tissues

Acute infections

rapid onset, fast viral replication, short duration

Persistent infections

slow and chronic, long-lasting, may remain dormant or react periodically

Prions

Infectious agents that cause fatal neuroldegenerative diseases

• do not contain nucleic acid

• comprised of misfolded proteins that are self-replicating

Prion reproduction

existing prions stimulate the conversion of normal cellular protein (PrPc) into a misfolded disease causing protein (PrPsc) that are resistant to proteinases

What is the SC in PrPsc

stands for "scrapie," a prion disease that was discovered in sheep

originally thought to be a virus - but after resisting heat, chemicals, UV, determined that scrapie lacked nucleic acid (unique to prions)

Human spongiform encephalopathies

caused by buildup in PrPsc in neurons leading to brain damage

Disease can be:

• acquired from environment

• genetic

• sporadic / spontaneous

Creutzfeldt-Jakob Disease (CJD)

fatal neural disease sure to PrPsc in brain leading to death of neurons

• a subset of spongiform encephalopathies

Can arise via:

• Sporadic CJD

• Genetic CJD

• Acquired CJD

Three types of CJD: Mad Cow Disease, Variant CJD (vCJD)

Sporadic CJD

arises from spontaneous PrPc → PrPsc change

Genetic CJD

inherited mutation in PRNP gene causing CJD

• specifically causes Gerstmann-Straussler-Scheinker Syndrome (GSS) and Fatal Familial Insomnia (FFI)

Acquired CJD

rare but involves human-human transmission

Mad Cow Disease

neurodegenerative disease of cattle

• in 1985, revealed to be new transmissible spongiform encephalopathy (Bovine spongiform encephalopathy - BSE)

• caused by cattle on high protein diets

Variant CJD

a form of Creutzfeldt-Jakob disease associated with the consumption of beef products contaminated with BSE

Mode of prion transmission

• ingestion

• blood transfusion

• treatments involving human cadaver products

  • contaminated surgical instruments

  • hormone replacements

  • brain tissue grafts

  • ocular tissue grafts

Herpes Simplex Virus (HSV)

Belongs to Herpesviridae family and Alphaherpesvirus subfamily

Includes:

• HSV-1

• HSV-2

• Varicella Zoster Virus

Virus has latent infection in sensory/peripheral neurons

Transmission via direct contact or body fluids

Similarities between HSV1 and HSV2

• double strand viruses

• replication occurs in host cell nucleus

• similar genomes

• both can cause oral and genital infections

Differences between HSV 1 and 2

HSV 1

• more commonly associated with cold sores

• often transmitted through oral-oral or oral-genital contact

HSV 2

• more commonly associated with genital infections

• often transmitted through sexual contact

Primary infection of HSV

break in skin/mucosa → virus accesses mucosa → infection in epithelial cells → virus replication → new viruses released → new viruses access sensory nerve endings to the sensory ganglions (retrograde transport)

Latent infection of HSV

occurs after primary infection

• virus is contained in non-replicative state within sensory neurons - hidden from immune system

• virus will later enter replicative state and travel from ganglion to sensory nerve endings (anterograde transport)

• this process ensure herpes for life

Human Papilloma Virus

a non-enveloped virus with ciruclar dsDNA genome (6-8 kilobase pairs)

• Contains 8 different gens in its genome

  • 6 early genes: E1, E2, E4, E5, E6, E7

  • 2 late genes: L1, L2

Transmission of HPV

Skin or mucosal contact

Infection is latent for 3-4 months before symptoms appear

• forms hyperproliferative lesions (cancerous lesion) and benign warts

Infection cycle of HPV

beings with abrasion of skin/mucosa that exposes basal membrane to epithelial cells → HPV is replicated within basal cells → expression of viral gene products as basal tissue differentiates and ascends into surface epithelia

Oropharyngeal HPV

spread through mouth-mouth or mouth-genital contact

often forms benign warts on lips, mouth, throat - can be cancerous in rare cases

Oral Papillomas

3 Types: Squamous papilloma, Verruca Vulgaris, Condyloma Acuminatum

Squamous Pailloma

Usually a single lesion on the lip, palate, or tongue

Verruca Vulgaris

Wart of gums - seem in children with warts on fingers that touch their mouth

Condyloma Acuminatum

Lesion on labial mucosa, lingual frenum, and soft palate

Oropharyngeal Squamous Cell Carcinoma

cancer found on pharyngneal walls, soft palate, base of tongue, tonsils.

72% of the time, this cancer is caused by HPV

Oral tuberculosis

Caused by Mycobacterium Tuberculosis

• Type IV Hypersensitivity (granulomatous inflammation)

• Primarily occurs in lung - occasionally progresses to tongue (uncommon)

• causes chronic ulcerations or swellings

Oral Syphilis

Caused by Treponema Pallidum

3 Three:

• Primary

• Secondary

• Tertiary

Primary Syphilis

Characterized by Chancre

• forms 3 to 90 days post infection

• mainly in genital areas but can also occur on lips

• Painless ulceration

Secondary Syphilis

Characterized by Mucous patches

• 4-10 weeks post infection

• systemic symptoms (fever, headache, malaise, pain, etc)

• Maculopapular cutaneous rash

Tertiary Syphilis

Characterized by Gumma (Granulomas)

• 30% of syphilis progresses to tertiary

• may cause perforation in the palate into the nasal cavity

• interstitial glossitis (lobular pattern on tongue)

• luetic glossitis (loss of lingual papillae on dorsal surface of tongue)

Oral Candidiasis

Caused by Candida Albicans and Erythematous Candidiasis

Associated lesions:

• denture stomatitis, Angular Cheilitis, Median Rhomboid Glossitis, Linear Gingival Erythema

Other types of Candidiasis

• Pseudomembranous Candidiasis (ORAL THRUSH)

• Chronic Hyperplastic Candidiasis

• Chronic Mucocutaneous (occurs on skin outside the oral cavity)

Other types of Herpes Viruses

• HHV 4: Epstein-Barr Virus → “mono"

• HHV 5: Cytomegalovirus (CMV) → opportunistic infections in immunocompromised patients

• HHV 6: Roseola → affects young children

• HHV 8: Kaposies Sarcoma → associated with HIV patients

Acute Herpetic Gingivostomatitis

Gingival ulcer that is caused by HSV 1 → painful, enlarged, red gingiva

• generally in infants and young children

Two types of fungal infections

Mold and Yeast

Mold

furry growth on surface of organic matter caused by fungi in for of multicellular filaments called hyphae

Yeast

single celled fungus that reproduce by budding

Things that increase risk of fungal infections

• Acute leukemia

• Neutropenia

• Immunosuppressive therapy

• Glucocorticoids

• Mucositis

• Central venous catheders

• Broad antibiotic use

• Genetics

• HIV

• Lung cavities

Antifungal drug mechanism of action

• target cell wall/membrane

  • ex,, Amforin B and Nystatin create pores in fungal cell wall

  • Azoles interfere with ergosterol (cell mem component) synth

  • Echinocandins also attack cell membrane

Oral Thrush

AKA pseudomembranous Candidiasis

• caused by candida albicans

• occurs in patients that overuse antibiotics or are immunodeficient

Local treatment: nystatin, Amphotercin B, Miconazole

Systemic Treatment: Fluconazole

Nystatin oral suspension

Take 4 times daily - 100,000 units → swish in mouth for as long as possible before swallowing

Drug class: polyenes

Mechanism: binds to sterol in fungal cell membrane and creates pores in cell membrane

Use: candida fungi

DDIs: none

Absorption: none

Amphotericin B lozenges

suck on 10mg lozenge 4 times daily

Miconazole oral gel

take 4 times daily, 2.5 ml - swish in mouth for as long as possible before swallowing

Treatment for Aspergillus Infection

Voriconazole loading dose → the maintenance dose

Alternatives:

• liposomal, Amphotericin B, lsavuconazole, posaconazole

Treatment of Candida infection

• Caspofungin (loading dose then maintenance dose)

• Anidulafungin (LD then MD)

• Micafungin

• Fluconazole (LD then MD)

Purpose of a loading dose

to quickly achieve a therapeutic level of a medication in the bloodstream before switching to a maintenance dose

Fluconazole

Drug class: Triazole

Mechanism of Action: inhibits ergosterol synth for cell wall formation

Use: against candida albicans

• treat oral thrush: 50-200 mg daily

• treating other invasive fungal infections:

  • LD up to 800 mg

  • MD up to 400 mg

DDIs: inhibits CYP3A4, 2C19, 2C9 enzymes

Dose must be adjusted depending on renal function

Voriconazole

Drug class: triazole

Mechanism of action: inhibits ergosterol for cell wall synth

Use: against Candida and Aspergillus infections

• treat invasive disease: 400mg LD or 6 mg/kg IV every 12 hours for the first 24 hours, then 200mg MD or 4 mg/kg IV every 12 hours

DDIs: inhibits CYP3A4, 2C19, 2C9

Adverse Effects: hepatotoxicity, hallucinations, rash

Posaconazole

Drug class: triazole

Mechanism of Action: inhibits ergosterol

Use: against candida and Aspergillus + Mucorales

DDIs: p-glycoprotein efflux substrate (reduces drug absorption)

Adverse effects: hepatotoxicity

Typical Characteristics of Fungi

• Eukaryotic

• lack chlorophyll therefore absorb nutrients from other organisms

• reproduce sexually (fusion of two fungi) and asexually (spores)

Reproduction of different fungi

Yeast: circular fungi that reproduce by budding

Pseudohyphae: reproduce by budding - budded cell attaches to parent to form chain

Hyphae: yeast cell that emits a tail-like projection for budding

Mating Projection: rare - cell extends appendage for mating

Yeast Cell Membrane

Plasma membrane made of ester-linked phospholipids and sterols

• outer wall contains mannose (pro-inflammatory)

• inner wall contains chitin and glucans

Name the oral candidiasis

Pseudomembraneous candidiasis

Name the oral candidiasis

Erythematous candidiasis

Name the oral candidiasis

Mixed candidiasis from Tc therapy

Name the oral candidiasis

Hyperplastic candidiasis

Name the candidiasis associated lesion

Denture Stomatitis

• Newton’s Type II (left)

• Newton’s Type III (right)

Name the candidiasis associated lesion

Angular cheilitis

Name the candidiasis associated lesion

Median Rhomboid Glossitis

Name the candidiasis associated lesion

Linear Gingival Erythema

Predisposing factors to oral candidiasis

• Physiological - age, pregnancy

• Local Trauma - mucosal irritation, poor OH

• Antibiotics - prolonged or broad use

• Corticosteroids

• Malnutrition

• Endocrine disorders

• Blood disorders

• Immune deficiencies

• Xerostomia

Reproduction of candida

Asexual: budding

Sexual: conjugation of haploids

Parasexual: conjugation of diploids

Yeast-Hyphal transition

Yeast is dormant → transitions in hyphal form which causes the infection

• hyphal form better evades immune system

Virulence traits of Candida albicans

1. Adherence

2. Invasion

3. Disarming host defence

Adherence of C. albicans

• Yeast agglutin-like sequence (ALS) proteins 1 and 5 bind to buccal epithelia and fibronectin

• hyphal proteins bind to buccal epithelia

• glycoproteins assist in anchoring to surface

Invasion of C. albicans

a) non-phagocytic cell endocytosis via Als3 Induction

b) active penetration with hyphae into host cells

Disarming host defense by C. albicans

1. downregulate epithelial TLR4 expression

2. aspartic proteases degrades C3b

3. inhibits phagolysosome formation

4. ROS inhibition

5. modulation of cytokine signals

Ways that hyphae can evade host immune system

A) if hyphae are phagocytosed, they can grow a hyphae through the phagocyte cell wall, leading to escape

B) hyphae reduces TLR4

C) hyphae blocks the complement system

D) prevents fusion between the phagosome and the lysosome - prevents phagolysosome formation

E) can modulate various immune cell function by modulating cytokine production