Human Papillomaviruses Flashcards
HPV belongs to the family of viruses known as ____________.
Papovaviridae [which was named for it’s three main genera: Papillomavirus, Polyomavirus, and Simian Vacuolating Agent]
Further notes:
The family contains two genera of oncogenic viruses, Papilloma and Polyoma viruses.
Briefly discuss the structure and genome type of human papillomaviruses.
Briefly describe the organisation of the genome of Papillomaviruses.
Papillomaviruses are small DNA viruses. The DNA genome is comprised of six early (E1, E2, E4, E5, E6, E7) and two late (L1 and L2) genes. The early genes are involved in viral replication and regulation of the host cell cycle, while the late genes encode the structural proteins necessary for assembling new virions [capsid proteins].
E6 and E7 are viral oncogenes. [Diagram]
Discuss the pathogenesis of HPV.
🛸 HPV infects the basal cells of the stratified epithelium, typically through micro-abrasions or wounds in the skin or mucosa.
Once inside the basal cells, HPV begins to replicate. The virus uses the host cell’s machinery to produce viral proteins and DNA.
🛸 HPV has evolved mechanisms to evade the host’s immune system. For example, the E5 oncoprotein downregulates the expression of MHC I molecules, helping the virus avoid detection by cytotoxic T lymphocytes.
🛸 The virus induces the infected cells to proliferate, leading to the formation of benign hyperproliferative lesions such as warts. In some cases, persistent infection with high-risk HPV types can lead to the development of precancerous lesions and, eventually cancer.
🛸 Persistent infection with high-risk HPV 16 and 18, can lead to the integration of viral DNA into the host genome. This integration disrupts normal cell cycle regulation, leading to uncontrolled growth and the potential development of cancers, such as cervical, anogenital and oropharyngeal cancers.
[Diagram 1] [Diagram 2] [Diagram 3]
State the function of the E2 protein and the effect of the disruption of the E2 gene.
The E2 protein acts as a transcriptional regulator, controlling the expression of other viral genes, including the oncogenes E6 and E7. By binding to specific DNA sequences in the viral genome, E2 can either activate or repress the transcription of these genes.
Integration of the HPV genome in the host cell chromosome usually disrupts E2 expression, causing deregulated expression of E6 and E7.
State the function of E6 protein.
E6 binds to the tumor suppressor protein p53 and targets it for degradation. This degradation prevents p53 from performing its normal function of inducing cell cycle arrest and apoptosis in response to DNA damage, allowing infected cells to proliferate uncontrollably.
Further notes:
E6 recruits the ubiquitin ligase E6AP (E6-Associated Protein) to target the tumor suppressor protein p53 for ubiquitination and subsequent degradation by the proteasome. This degradation of p53 prevents apoptosis, allowing infected cells to proliferate uncontrollably, which can lead to cancer.
State the function of E7 protein.
E7 protein disrupts the function of the retinoblastoma protein (pRb), promotes cell cycle progression, interferes with other cellular proteins, induces genomic stability, and modulates the immune response.
How are HPVs categorized?
HPV types are categorized into low-risk and high-risk strains. Low-risk types cause genital warts, while high-risk types can lead to cancers.
What are the high-risk variants of HPV responsible for 70% of all cervical cancers worldwide?
16, 18
What are the low risk variants of HPV responsible for 90% of genital warts?
6, 11
How is HPV transmitted?
HPV is primarily spread through intimate skin-to-skin contact, including vaginal, anal, and oral sex. It can also be transmitted from mother to child during childbirth.
Which cancers are associated with high-risk HPV types?
High-risk HPV types can cause cervical, anal, penile, vulvar, vaginal, and oropharyngeal cancers.
List common clinical manifestations of HPV infection.
[Human papillomavirus (HPV) infections often do not cause any noticeable symptoms, especially in the early stages. However, when symptoms do appear, they can vary depending on the type of HPV involved. Here are some common signs and symptoms associated with HPV:]
(1) Genital warts: small bumps or flat lesions
Location in women: vulva, cervix, vagina, or around the anus Location in men: penis, scrotum, or around the anus
[Image 1] [Image 2]
(2) Common warts: rough, raised bumps
Location: typically on the hands and fingers.
[Image]
(3) Plantar warts: hard, grainy growths
Loction: soles of feet
[Image]
(4) Flat warts: flat-topped, slightly raised lesions
Location: can appear anywhere on the body but are more common on the face, neck, hands, wrists, and knees
Symptoms: generally painless
[Image 1] [Image 2]
(5) Cervical dysplasia:
Appearance: Abnormal precancerous cells on the cervix. [Image]
Symptoms: Usually asymptomatic and detected through routine Pap smears.
(6) Oropharyngeal lesions:
Appearance: lesions in the mouth or throat
Symptoms: can include sore throat, ear pain, and difficulty swallowing
(7) Cancer: cervical, anal, penile, vulvar/vaginal, oropharyngeal
Laboratory diagnosis of HPV
What is HPV DNA typing?
HPV DNA typing involves detecting the presence of HPV DNA in a sample, typically using PCR to identify specific HPV DNA sequences and determine the HPV type.
Laboratory diagnosis of HPV
What does the detection of E6 and E7 mRNA indicate?
Detection of E6 and E7 mRNA indicates active viral replication and integration into the host genome, which is a marker for potential progression to cancer.
Further notes:
High-risk HPV types express the E6 and E7 oncogenes, which are involved in the disruption of tumor suppressor proteins like p53 and Rb.
