Exam #6: Viral STIs

Question 1

List the characteristics of HIV. What is the difference between HIV-1 & HIV-2?

Answer 1

Retroviridae 
\+ssRNA
Enveloped
2 Types= HIV-1 & HIV-2 (HIV-1 is more common worldwide & HIV-2 is more endemic to West Africa
- Slower decline in CD4 T-cells
- Longer asymptomatic period
- Lower mortality 

Note that the genome consists of a homodimer of two identical sequences; thus, it is functionally diploid.

Question 2

Describe the structure of HIV. What proteins are associated with each part of the HIV structure?

Answer 2

+ssRNA (2x copies)

Enveloped= gp120 (attachment) & gp41 (fusion)

Matrix protein= p17

Nucelocapsid= p24

Genome= pol gene that encodes reverse transcriptase

Question 3

List the stages retrovirus lifecycle.

Answer 3

Attachment (gp120)
Fusion (gp41)
Reverse transcription (pol gene)
Integration (integrase)
Transcription of provirus 
New genome & mRNA 
Budding

Question 4

How does HIV attach? What cells does HIV attach to?

Answer 4

• gp120 binds CD4
• CD4 is found on T-lymphocytes, monocytes, & macrophages
• Conformational change in gp120 to allow binding to co-receptor (CCR5 or CXCR4)

Question 5

What is the difference between R5-tropic HIV & X4-trophic HIV?

Answer 5

After attachment, gp120 undergoes a conformational change that allows binding to a co-receptor

• CCR5= person to person transmission
• CXCR4= more rapid progression to AIDS

Question 6

What is the significance of CCR5 deletions in HIV?

Answer 6

Deletion in the CCR5 gene augments disease pathogeniticity

• Heterozygous= longer asymptomatic to R5
• Homozygous= no infection with R5 (1% of the Caucasian population)

However, can be infected with CXCR4

Question 7

How does HIV fuse with the plasma membrane?

Answer 7

Gp41 mediates fusion between the viral envelope & plasma membrane by bringing the two close together

Question 8

What codes for Reverse Transcription? What is the function of Reverse Transcriptase?

Answer 8

• pol gene
• Produces dsDNA linear copy of RNA HIV

*Note that this is associated with a high error rate because this is what allows for rapid evolution during the time course of disease e.g. resistance to antivirals

Question 9

How does HIV integrate into the host genome?

Answer 9

• dsDNA moves into the nucleus
• viral integrase causes DNA copy to be incorporated into the host DNA

Viral DNA integrated into the host genome is called “provirus”

Question 10

How does HIV egress?

Answer 10

• Viral envelope proteins are incorporated into the plasma membrane to form lipid rafts
• Virions acquire envelope as they bud from the cell, giving the the appearance of spheres with an electron dense ring surrounding

Question 11

What is maturation?

Answer 11

Virion maturation= viral protease cleaves gag & gag-pol that is essential for infectivity

Question 12

How is HIV transmitted? What is the risk associated with each mode of transmission?

Answer 12

Sexually

• Male-to-female is most effective
• Most common route
• Presence of other STIs increases risk

Perinatal= 1/4

• 25-30% before birth
• 50-65% at birth i.e. HIGHEST at birth
• 12-20% during nursing

Exposure to blood or body fluids

• Needle stick= 0.3%
• Mucous membrane= 0.09%

Note that the exposure risk to healthcare workers is less than that of Hepatitis B & C

Question 13

What are the difference stages of HIV infection?

Answer 13

• Acute Infection= mononucleosis-like symptoms
• Chronic Phase= host immune response curtails plasma viremia; asymptomatic but chronic lymphadenopathy
• AIDS= opportunistic infections

Question 14

Draw the graph of viral load, CD4 T-cell, & anti-HIV antibody through the course of the disease.

Answer 14

N/A

Question 15

What symptoms are seen in acute HIV syndrome?

Answer 15

3-6 weeks post infection

Fever
Malaise
Arthralgia 
Lymphadenopathy 
Sore throat 
Rash 

*May not have detectable levels of anti-HIV antibodies at this time.

Question 16

What are the characteristics of chronic HIV infection?

Answer 16

• Low viermia
• HIV escape from immune response
• Patient asymptomatic

10 years in the absence of antivirals

Question 17

What is the HIV-set point? Why is it important?

Answer 17

Level of the virus in the blood 1 year following infection

• Lowest= fewest individuals progressing to AIDS in 10 years following infection
• Highest load= most individuals progressing to AIDS in 10 years

Question 18

How does HIV kill T-cells?

Answer 18

• Copious budding
• Interference with cellular processes
• Other mechanisms

Question 19

How is AIDS defined?

Answer 19

CD4 T-cell count less than 200

Question 20

List some common HIV associated infections.

Answer 20

• Oral Hairy Leukoplakia
• Peumonia
• Thrush
• CMV retinitis
• Neoplasms
• Diarrhea

Question 21

What causes Oral Hairy Leukoplakia?

Answer 21

EBV

Question 22

What causes HIV associated Pneumonia?

Answer 22

Pneumocystis carinii

Mycobacterium tuberculosis

Question 23

What causes HIV associated Thursh?

Answer 23

Candida albicans

Question 24

What causes HIV associated CMV retinitis?

Answer 24

Cytomegalovirus

Question 25

What causes HIV associated Neoplasms?

Answer 25

Kaposi's sarcoma | B-cell lymphomas

Question 26

What causes HIV associated diarrhea?

Answer 26

Cryptosporidium | Isopsora belli

Question 27

Draw the sequence & appearance of laboratory markers for HIV-1 infection.

Answer 27

1) HIV-RNA 2) HIV-1 p24 antigen 3) HIV antibody

Question 28

Draw the algorithm for HIV testing.

Answer 28

1) Screen (HIV 1/2 antigen/antibody immunoassay for HIV p24 antigen & HIV1-2 antibodies) 2) Confirmatory test to differentiate HIV-1 & HIV-2 3) If negative or indeterminate, then nuclei acid testing to detect RNA genome

Question 29

How is HIV NAAT used?

Answer 29

To follow the course of antiretroviral treatment

Question 30

What are the different classes of anti-retrovirals?

Answer 30

``` Entry inhibitors or chemokine coreceptor antagonists Fusion inhibitors Reverse Trascriptase Inhibitors Integrase Inhibitors Protease Inhibitors ```

Question 31

Describe the mechanism of action of the Entry inhibitors.

Answer 31

Chemokine receptor antagonists | - Bind to the co-receptor (CCR5 or CXCR4) & prevent interaction with gp120

Question 32

Describe the mechanism of action of the Fusion inhibitors.

Answer 32

- Bind gp41 & prevent conformational change needed for fusion of the viral envelope with cellular plasma membrane

Question 33

Describe the mechanism of action of the Reverse Transcriptase Inhibitors.

Answer 33

NRTIs i.e. "Nuceloside reverse transcriptase inhibitors" - Nucloside analogs incorporated into the growing DNA chain during synthesis of provirus & cause early termination NNRTIs i.e. "Nonnucleoside reverse transcriptase inhibitors" - Reverse transcriptase antagonists

Question 34

Describe the mechanism of action of the Integrase Inhibitors

Answer 34

Inhibit viral integrase to prevent DNA incorporation/ formation of the provirus

Question 35

Describe the mechanism of action of the Protease inhibitors.

Answer 35

Act on the enzyme needed to cleave gag & gag-pol during virion maturation

Question 36

What is the standard of care for ARV therapy?

Answer 36

Combination of drugs from three classes - 2x NRTIs + 1) NNRTI 2) PI 3) II