Viral Infection and Pathogenesis Flashcards Preview

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Flashcards in Viral Infection and Pathogenesis Deck (19):
1

Primary types of transmission

Vertical: transmission from parent to offspring in utero
• Requires viremia, ability to cross placenta
• Most common during primary infection of mother
• Ex: congenital Rubella or CMV

Horizontal: transmission from one individual to another
• Most infections

2

List the 6 types of horizontal transmission

Respiratory
Fecal-Oral
Close contact
Insect vector
Animal vector
Direct injection

3

Respiratory transmission

• Most common
• Also able to enter through conjunctiva
• Can be used by viruses not causing respiratory infections (measles)
• Spread via wet secretions that contaminate environmental surfaces
• Many viruses able to survive for days
• Also spread via sneezing = disperses fine particles into air
• Higher incidence in winter

4

Fecal Oral Transmission

• Common (though incidence is under-reported)
• Large amounts virus shed in feces
• Many = resistant to killing (survive long periods in environment)
• Heat resistant
• Protease resistant
• Can be alcohol-resistant
• Require higher bleach concentrations to kill
• Can be used by viruses that don’t cause diarrhea
• Most U.S. outbreaks due to contaminated food or water
• Ex: Rotavirus diarrhea, Poliovirus

5

Transmission by close contact

• Viruses = labile or shed in low amounts
• Most commonly by kissing or sex; can be via fomites (ex: HPV) or nursing
• Type used by many persistent viruses

6

Insect vectors

• >400 viruses
• Mosquitos = most common; also via ticks
• Requires virus be able to replicate in both host and insect (broad host range)

7

Animal Vectors

• Bats very important
• Many considered “emergent” infections (Ebola virus, Lassa fever, Sin Nombre, SARS Coronavirus)
• Usually highly lethal because humans not natural host
• Requires virus replicates in animal vector
• Transmission via: bites, feces, contaminated urine, or butchering a carcass
• Ex: rabies

8

Transmission by Direct Injection

• Usually by contaminated needles
• Requires viremia in source host
• Common in IV drug users = needle sharing programs reduce transmission but do NOT eliminate due to cultural/social factors
• At risk = health care workers

9

Discuss viral entry into a host, including the most common entry sites

• Majority = via respiratory route
• 2nd most common = via GI tract
o Ex: polio virus or Coxsackie virus (both enter through GI but not cause GI symptoms)
• Next = via mucous membranes (genitalia or mouth) or close contact
By animal vectors:
o Direct injection through skin by mosquitoes
o Defecation of insect followed by scratching
o Inhalation of dried urine or feces (ex: Hantaviruses, Lassa fever virus)

10

Describe the processes involved in the spread of virus through the host in the two basic types of infections (local and disseminated).

Localized Infection.
o Virus remains localized at the site of entry
• Ex: Herpes simplex virus cold sores, Human papillomavirus warts
o Most respiratory viral pathogens (URT or LRT)
o Though virus remains localized, systemic symptoms can result (Influenza muscle aches and fever)
o Can spread in those who are immunocompromised

Disseminated infection.
o Virus spreads throughout the host following entry (usually via lymphatics)
• Must be able to penetrate basement membranes
o Multiple organs and tissues can be infected
Process:
• Localized replication in epithelial cells
• Virus spreads to lymphatics
• Small amounts of virus seed blood = Primary Viremia
• Transient and low titer
• Other cells (permissive cells), tissues, and organs are infected = Secondary Viremia
• Higher titer and more sustained
• Target tissues or organs now infected (liver, brain etc.)
• Development of specific symptoms
• Chance of developing symptoms increases with higher titer and duration of secondary viremia

11

Describe ways in which viruses directly damage cells and relate this to the causation of symptoms.

Host shut-off: infection → shutting down host gene expression
o Some viruses = severe host shut-off → direct killing of infected cells
o Other = selectively inhibit expression of specific host proteins

Inhibit host translation
o Major mechanism
Mechanisms:
• Altered phosphorylation of host initiation factors
• Proteolytic cleavage of host initiation factors
• Digestion of host mRNA

Inhibit host gene expression
o Block transcription of host genes by affecting DNA dependent RNA polymerase (Pol II)
o Interfere with splicing of host mRNA
o Interfere with transport of host mRNA to cytoplasm

Interfere with cell cycle
o Shutoff of host gene expression = stops the cell cycle
o DNA viruses cause cells to enter S phase = Stop it just before the cellular DNA actually replicates
o Entering S phase → increased expression of proteins and nucleoside substrates used in DNA replication
• The cells make more “goodies” for the virus to use

Apoptosis
o Viral infections triggers apoptosis
Good: defense mechanism
• Cell death before assembly stops infection
• All viruses encode functions to block apoptosis
• Anti-apoptotic functions have role in human cancer
Bad: some viruses activate apoptosis to help virus get out of cell and spread

Cell transformation

12

Define cytopathic effect and be able to list examples.

Viral infection resulting in changes in cell shape:
o Shrinkage of cell nucleus

o Cell rounding and detachment from plate (From disrupted tight junctions and actin cytoskeleton)

o Development of inclusion bodies (aggregations of viral material or virions)
• Can be nuclear or cytoplasmic
• Eosinophilic or basophilic
Can be diagnostic
• Ex: Negri bodies in rabies
• Ex: Owl eye cells in Human CMV

o Cell-cell fusion (syncycium formation)
• Induced by enveloped viruses = infected cells fuse with adjacent uninfected cells → forms multi-nucleated cells
• Ex: HSV, Respiratory Syncytial Virus
• Allows for spreading in presence of neutralizing antibodes

13

Discuss the differences between acute and persistent infection.

Acute Infection
o Host acquires virus
o Host defenses respond
o Host clears virus
o Ex: common cold, influenza virus

Persistent Infection
o Host acquires virus
o Host defenses respond
o Defenses not able to clear virus
o Host infected for life or long period
NOTE: high percentage of viral infections are subclinical

14

Describe the differences between latent and chronic infection. What is the most significant difference between the two patterns?

Both = types of persistent infections:

Chronic Infections
• The presence of isolatable infectious virus lasting longer than 6 months after initial infection
• Ex: Hepatitis B and C viruses
• Persons are infectious at all times (environmental source)

Latent Infections
• Virus cycles between periods where infectious virus is shed and the person is infectious and times when no infectious virus can be detected.
• Reactivation = virus shed asymptomatically
• Recrudescence = viral replication associated with symptoms
• Ex: Herpes, Adeno-, Papilloma, Papova-, and Parvoviruses
Note: HIV exhibits BOTH patterns

15

Acute vs. Chronic cancer viruses

Acute cancer viruses
o Encode directly transforming genes
o Short incubation period
o Tumors are polyclonal
o Several tumors can occur at the same time in a host
o Ex: Kaposi’s Sarcoma (HHV8)

Chronic cancer viruses
o Immortalize cells
o Additional mutations required for cancer
o Long incubation period
o Tumors are monoclonal
o Ex: HPV induced cervical cancer

16

Define: productive infection, permissive cell, and abortive infection.

• Productive infection = Infectious virus is produced
• Permissive cell = A cell that supports the complete replication cycle
• Abortive infection = Non-productive, no infectious virus is produced
• Non-permissive cell = A cell that does not support replication and produce infectious virus

17

Define: primary cells, immortalized cells, and transformed cells

Primary cells = Cultured directly from host tissue or organ and have a limited lifespan
• Enter senescence after several cell divisions

Immortalized cells = Mutant primary cells that overcome senescence
• Grow continuously
• Do not cause tumors when injected into animals

Transformed cells = Mutant immortalized cells
• Lose anchorage independence and form tumors when injected into animals
• Cell culture model for cancer but generally are not metastatic

18

Describe the mechanism of the viral cancers

Majority = primary mechanism is to promote cell growth and division (immortalize)
o Mutations occur over time (in proto-oncogenes) → cancer cell
Result: most viral cancers:
• Long incubation
• Clonal (originated from 1 cell)

Exception: Kaposi’s Sarcoma
o Caused by HHV-8 virus
o Virus encodes genes that directly transform endothelial cells
o Result: multifocal cancer (multiple tumors appear at same time in multiple places in body)
o Shorter incubation

19

Recognize the association between some viral infections and human malignancies. Be able to list which virus is associated with the malignancies.

Human T-cell Leukemia virus (HTLV-1) = adult T cell leukemia

Hepatitis C & B virus = hepatocellular carcinoma

Epstein-Barr virus = Burkitt's Lymphoma, Nasopharyngeal carcinoma, American Burkitt's, B cell lymphomas, GI cancers

Human Herpes Virus-8 = Kaposi's Sarcoma, Castlemen's Disease, Primary Effusion Lymphoma

Human Papilloma virus = cervical, penile, vaginal, and anal carcinoma, skin carcinomas, and others

Merkel cell tumor polyoma virus = Merkel Cell carcinoma

Human Cytomegalovirus = possible role in glioma

JC virus = Possible role in colorectal cancer