Busm Id- Lec 18 Virus Path And Lab Diagnostics

Front 1

Lecture 18
Learning Objective 1:


Describe the differences between abortive, lytic, and persistent virus infections of cells.

Back 1

1. Abortive infection: a failed infection= no viral replication.

2. Lytic infection: results in cell death (lysis)
-Often due to inhibition of host cell macromolecular synthesis.

-Viral replcation can disrupt cell structure/fxns-->inculsion bodies can form in the nucleus or cytoplasm

-Viral proteins on cell surface can elicit immune-mediated cytolysis (seen in HepB)

-Induction of apoptosis (but viruses actually have mechanisms that can hold this off long enough for them to replicate)

-Formation of syncytia (mulitnucleated giant cells)

-Cytopathic effects (CPE)= inculsion bodies, apoptosis, and syncytia can be used to dectect viral infection in lab tests.

3. Persistant infection: an infection that persists with little or no cell death. Classified as chronic, latent or transforming.

Front 2

Lecture 18
Learning Objective 2:

Describe the differences between chronic, latent, and transforming persistent viral infections of cells.

Back 2

a. Chronic: productive but non-lytic; virus release by
budding.
b. Latent: limited/no viral gene expression.
-no virus production.
-virus production can often be re-activated.
**Herpes stay for life!
c. Transforming: immortalization of cell by oncogenic
viruses.

Front 3

Lecture 18
Learning Objective 3:

Describe the difference between an acute and a chronic infection of a patient.

Back 3

Acute= infection is completely cleared from body
Persistant= virus is not cleared from body and may either persist with viron production until death, or become latent and only make viruses periodically during reactivation.

Front 4

Lecture 18
Learning Objective 4:

List and explain the basic steps in the production of viral-induced disease in the body.

Back 4

Basic Steps in Viral Pathogenesis
1. Entry into the body
2. Replication
3. Incubation period&Disease Production
4. Convalescence (recovery)

Front 5

Lecture 18
Learning Objective 4:

List and explain the basic steps in the production of viral-induced disease in the body.

1. Entry into the body

Back 5

Locations of entry:
- Skin
- Respiratory tract (major site of entry)
- GI tract (also major site) but envelope viruses are prone to breakdown by the hostile environment of the upper GI
- GU tract- sexually transmitted viruses: HSV, HPV, HBV, HIV
- Conjuctiva- direct contact, swimming pools...

Viruses may stay localized at the site of entry or they may spread and become systemic.

Front 6

Lecture 18
Learning Objective 4:

List and explain the basic steps in the production of viral-induced disease in the body.
2. Replication

Back 6

Primary replication occurs at the site of entry in PERMISSIVE cells= can only replicate in cells that allow it.

Localized infections replicate and remain at the site of entry

Front 7

Lecture 18
Learning Objective 4:

List and explain the basic steps in the production of viral-induced disease in the body.

3. Incubation period and spread of virus

Back 7

Incubation: The time interval between infection of the host and onset of clinical symptoms (not inculuding prodrome).

A. Virus is amplified and possibly spread to secondary site to become a disseminated/systemic infection

B. It may be asymptomatic, associated with the prodrome (nonspecific, early flu-like symptoms, or symptomatic!

Spread of virus:
1. Local spread on epithelial surfaces
2. Subepithelial spread and lymp invasion
3. Bloodstream= viremia--> most effective means of spreading
-Primary viremia (low titer)= b/c of replication at primary site
-Secondary (high titer)= b/c of replication at a secondary site
-Virus may be free in the blood or cell associated
4. Perpherial Nerves (like herpes, varicella, and rabies)

Front 8

Lecture 18
Learning Objective 5:


List the 5 major sites of viral entry into the human body and protective mechanisms at each site that inhibit viral entry/attachment or inactivate viruses.

Back 8

Locations of entry:
1. Skin- thick layer of dead keratinized cells, basement membrane

2. Respiratory tract (major site of entry): sticky mucus layer, ciliated cells, lymph nodes, cooler temp of nose and upper respiratory prevents viral replication.

3. GI tract (also major site)- upper GI is harsh environment= low PH, protases, bile salts, mucus with IgA. **envelpe viruses are particullary susseptible to being deactivated here**

4. GU tract- sexually transmitted viruses: cervical mucus, PH of vaginal secreaions, chemical composition of urine.

5. Conjuctiva- blinking and tears help prevent attachment and entry.

Front 9

Lecture 18
Learning Objective 6:


List 4 ways in which viruses can spread from their site of entry to target tissues in the body.

Back 9

Spread of virus:
1. Local spread on epithelial surfaces
2. Subepithelial spread and lymp invasion
3. Bloodstream= viremia--> most effective means of spreading
-Primary viremia (low titer)= b/c of replication at primary site
-Secondary (high titer)= b/c of replication at a secondary site
-Virus may be free in the blood or cell associated
4. Perpherial Nerves (like herpes, varicella, and rabies)

Front 10

Lecture 18
Learning Objective 7:



Define incubation period.

Back 10

Incubation: The time interval between infection of the host and onset of clinical symptoms (not inculuding prodrome).

A. Virus is amplified and possibly spread to secondary site to become a disseminated/systemic infection

B. It may be asymptomatic, associated with the prodrome (nonspecific, early flu-like symptoms, or symptomatic!

Front 11

Lecture 18
Learning Objective 8:

Explain the main factors that determine viral cell and tissue tropism.

Back 11

Viruses require the presence of specific receptors, transcription factors, proteolytic enzymes, and other factors for replicaiton and pathogenesis. If these factors are not present, the virus cant replicate. Each virus has different requirements and this limits the cell types that each can replicate in.

Front 12

Lecture 18
Learning Objective 9:

List the factors that affect the susceptibility and severity of disease in an individual and describe why they do so.

Back 12

Virulence refers to the ability of a virus to cause illness or death in an infected host relative to other strains of the same agent. Virulence is not an absolute property of a virus strain-it depends on both host and viral factors:
a. nature of the exposure (route of infection).

b. immune status, age, and general health.

c. viral dose.

d. genetics of the virus and the host.

e. ability of the host to repair damage.

Front 13

Lecture 18
Learning Objective 10:

Explain the importance of, and rationale for, proper specimen collection and processing

Back 13

Want to know what virus is causing disease in your patient because:

1. There are treatments for some infections (but not all).
2. IDing the virus allows for accurate prognosis, treatment of symptoms and prevention of spread.
3. IDing the virus provides important epidemiological info and helps with vaccine development.

Front 14

Lecture 18
Learning Objective 11:


Explain the difference between a presumptive and a definitive identification/diagnosis.

Back 14

A preseumptive diagnosis is your "best guess". It is made based on the clinical picture matched with lab evidence of cytopathic effects (CPE's). For example if some one comes in with a clinical picture consistant with a herpes infection, and you see in a cell culture syncytia it's probably herpes b/c only flu, measles and herpes viruses make syncytia (mostly).

Other techniques used to make a presumptive dx-
Presence off incusion bodies, apoptosis, deformed cells....
Hemeadsorption
Hemeagglutination

A definitive diagnosis- can only be made through the detection of virus SPECIFIC antigens and/or genomes!

Front 15

Lecture 18
Learning Objective 12:

Define “cytopathic effects” and describe 3 examples

Back 15

Cytopathic effects: when viral replication in a host cell causes the cell to change.

1. Syncytia= multinucleated giant cells
2. Inclusion bodies= viral "factories" often formed in nucleus or cytoplasm.
3. Induction of apoptosis

Front 16

Lecture 18
Learning Objective 13:


Explain the differences between viral culture and techniques that directly detect virus in clinical specimens with respect to relative sensitivity and time needed to get results.

Back 16

Viral cell culture:
requires infectious, growth competent virus.
Advantages: SENSITIVE, simple, "open-minded". Amplifies virus for use in other assays.
Disadvantages: SLOW, some viruses dont grow in culture, have to pick the appropriate cell line.

Detection of virus in clinical specimen:
Detects virus particles, protiens or nucleic acids
Advantages: FAST, does NOT require infectious or growth compentent virus
Disadvantages: LESS SENSITIVE, sample might not contain enough viruses to be detected, must choose the right virus specific reagents..

Front 17

Lecture 18
Learning Objective 15:


Describe how serology can be used to determine whether a patient has a current (recent) viral infection or has had a specific viral infection in the past.

Back 17

IgM antibodies indicate the infection is recent.

IgG antibodies indiacte a past infection.