L10: Genitourinary infections Flashcards Preview

Medical Virology (UoG) Midterm 2 > L10: Genitourinary infections > Flashcards

Flashcards in L10: Genitourinary infections Deck (20):
1

Which STDs cause disease in the genital tract? (2)

- HIV
- HSV types I and II (approx 85% is type II though)
Note that other STDs are shed in genital secretions but do not cause infection in the GT itself

2

What is the difference between high and low risk HPV?

High risk is often associated with anogenital cancers (eg cervical, penile, etc), whereas low risk HPVs indice benign genital warts.

Low risk HPV E6 and E7 proteins have lower affinity for Rb and p53 proteins. Not surprisingly, high risk HPV has a lot of potential to transform cells into cancer cells.

3

Which subtypes of HPV are the ones we need to worry about?

- HPV 6 and 11 --> responsible for approx. 90% of anogenital cancers
- HPV 16, 18 --> 80% of cervical cancers

4

Is it possible to clear HPV without treatment?

Sure is! Usually takes several months, up to a year.

5

How is HPV transmitted?

- skin to skin
- vaginal
- anal
- oral
- vertical (very rarely)

6

What do the HPV E6 and E7 proteins do?

- Helps to evade the tumour supressor proteins p53 and Rb (retinoblastoma)
- E7 binds to hypophosphorylated Rb and prevents transcription factor E2F binding (free E2F promotes transcription and pushes cell back into the cell cycle)
- E6 binds E6-AP and degrades p53. It also induces telomerase activity and immortalises cells.

7

How can HPV be detected?

- characterised by presence of koilocytes (enlarged nuclei with halo structures around them), hyperchromasia (inc keratin)

8

How does HPV interact with the immune system?

- It deosn't!
- made an effort to evolve not to infect APCs, not cause cell lysis or viraemia

9

How does the body clear HPV?

- smallish innate IR, just enough to stimulate CTLs that target E2, E6 and E7 proteins
- it takes >8months to clear since the IR isn't strong

10

What risk factors are there for HPV transformed cervical cancers? (5)

- >5 years use of oral contraceptives
- smoking
- >5 full term pregnancies
- previous exposure to STDs like HSV II and chlamydia
- defective IR

11

How is HPV diagnosed?

- 30% of infections by observation --> genital warts
- can be based on abnormal pap smear results
- HPV DNA test

Note: HPV cannot be grown in the lab or screened in blood

12

How can HPV be treated?

Warts:
- can be cleared without outside help
- freezing
- burning
- laser
- surgery
- IFNα injections

13

What other types of cancers (not anogenital) can HPV cause?

- Head and neck (thought to be up to 90% caused by HPV16)
- Lung cancers (very questionable though, 15-20% in men and up to 50% in women, all non-smokers)

14

What vaccine(s) is/are available for HPV?

- Gardisil
- 9-valent (6, 11, 16, 18, 31, 33, 45, 52 and 58) from yeast
- VLPs from L1 capsid protein (self assembles)
- very effective, no risk of HPV infection (since its a VLP)

- Cerverix
- uses L1 protein of HPV 16 and 18
- Generates higher antibody levels than Gardisil
- VLPs produced from baculovirus

15

What are some general characteristics of Herpesviruses?
- genome sense and type
- enveloped?
- other host species?
- # of subtypes
- transient or persistent?

- dsDNA
- cause persistent infection (lytic and latent cycles)
- enveloped
- ubiquitous across all vertebrate species
- 8 subtypes
α-herpes = HSV1, HSV2, VZV (infects neurons)
β-herpes = CMV (cytomeglavirus), HHV6 (human herpes virus), HHV7 (infects B cells)
γ-herpes = EBV (epstein barr virus) and HHV8

16

What are some clinical features of HSV1, 2 infection?

- 2x distinct clinical patterns: primary infection and recurrent infection
- takes 1-3 days to develop vesicles (in clinically apparent cases)
- Virus may disseminate in immunocompromised individuals
- Blisters will ulcerate than shed

17

How are herpesviruses classified?

According to their location in the latent state:
- Alpha-herpesviruses (HSV1,2, VZV) in neurons
- Beta-Herpesviruses (CMV, HHV6, 7) in B lymphocytes
- Gamma-herpesviruses (EBV, HHV8) in monocytes/lymphocytes

18

What factors contribute to HSV reactivation?

- local trauma (surgery)
- exposure to strong sunlight
- fever
- systemic stress

19

What mechanisms contribute to HSV latency?

- Latency associated transcript (LAT) = no protein product associated with it
- miRNA encoded by LAT confers resistance to apoptosis
- miR-LAT downregulates TGFB1 (transforming growth factor) and SMAD3 expression - both are related to the TGFB apoptosis pathway

20

How does HSV infection work?

- Primary infection in epithelial cells
- Virus travels retrograde up sensory ganglia and lives here even after epithelial lesions heal (latent infection)
- Reactivation involves the orthograde transport of the virus down neurons back to the original site of infection (productive epithelial cell infection)