Study Notes on Papillomaviruses and Herpes Viruses

An accident can occur when there is a prolonged presence of papillomavirus DNA in human cells.
This prolonged presence increases the likelihood of abnormal cellular changes over time which can lead to cancer.

Integration Mechanism: Papillomavirus DNA can integrate into host cell's chromosome.
If integrated in an unfavorable manner, it can cause significant changes in cellular growth leading to cervical cancer.
Transmission: The initial viral infection happens years before cancer develops, with viral presence often diminishing over time.

The presence of certain viral proteins, specifically E2, plays a key role in moderating the expression of other vital oncogenes, E6 and E7.
- E2 protein restrains transcription of E6 and E7, limiting their expression.
- E6 and E7 promote progression through the cell cycle, aiding in viral replication.
Misregulation Effects: If the E6 and E7 coding regions integrate into the chromosome without the regulatory E2, they may be overexpressed.

Normally, E6 and E7 share a single mRNA that is unstable and rapidly degraded due to a destabilizing sequence located at the 3' end.
Random integration could disrupt this sequence, resulting in a stable mRNA that might lead to overproduction of E6 and E7 proteins, increasing cancer risk.

Persistence of E6 and E7: Cells may permanently express high levels of E6 and E7, which contributes to cervical cancer risk, surpassing those from just being virus-infected cells.

Vaccine Overview: Cervical cancer prevention through vaccination against high-risk HPV types.

Mechanism: Vaccines use L1 protein that forms virus-like particles (VLPs), mimicking the native virus.
- VLPs are highly immunogenic, eliciting a robust immune response without containing viral nucleic acids, making them non-infectious.
Advantages of VLPs:
- Provides a better immune response than using proteins that do not resemble the actual infection context.
- Safety advantage as VLPs cannot revert to an infectious form.

Approval and Mechanism: Approved FDA in 2006, targets HPV types 6, 11, 16, and 18.
Quadrivalent Vaccine: Mixture of four types targeting HPV strains associated with cervical cancer and genital warts.
- HPV 16 and 18 - account for ~70% of cervical cancer.
- HPV 6 and 11 - contribute to benign warts, no cancer risk.
Vaccination Timing: Recommended before sexual activity initiation to maximize effectiveness due to high prevalence of HPV.

Gardasil 9: An improved formulation that protects against 9 HPV types, covering 90% of cervical cancers.
- Effective in preventing persistent infections and precancerous lesions.

DNA Testing: Improved methodology for detecting HPV DNA in patient samples is becoming common.
Pap Smear Testing: Continued importance for women vaccinated against HPV due to other cancer-linked HPV strains.

Vaccines held to high standards for efficacy and safety.
Concerns regarding misconceptions about vaccine-induced immunity necessitate continued screening for cancer risk due to remaining types.
Importance of public health communication regarding vaccine limitations and screening needs.

Concept: Targeting E6 and E7 to stimulate immune responses against infected cells post-cancer diagnosis rather than preventive vaccination.
Potential use in retroviral infections, drawing parallels with rabies post-exposure vaccination techniques.

Transitioning to different viruses; focussing on herpes and pox viruses for their significant clinical relevance.

Genome and Structure: Large linear double-stranded DNA genome, icosahedral capsid, lipid envelope with glycoproteins.
Replication: Occurs in the nucleus of host cells.

Herpes Simplex Viruses (HSV):
- HSV-1: Causes cold sores.
- HSV-2: Genital lesions; prevalent sexually transmitted infection.
Varicella-Zoster Virus (VZV):
- Causes chickenpox and shingles.

Characteristics: Establishes latent infections where virus remains dormant in neurons, escapes immune detection, and can reactivate later.

Infection Mechanism: Epithelial cell infections are productive, whereas neuronal infections lead to latency.
How latent infections reactivate is poorly understood but may relate to host stress or immune responses.

No cure for herpes; primarily managed with antiviral drugs (e.g., acyclovir).
- Acyclovir Mechanism: Mimics nucleosides, terminating viral DNA synthesis post incorporation.
- The specificity of activation through viral kinases ensures minimal effects on host cells.

Episodic vs. Suppressive Therapy: Strategies to manage outbreaks and reduce transmission risk.
Valacyclovir as a more absorbable prodrug formulation of acyclovir.

Pox viruses, such as variola virus, exhibit unique replication strategies entirely in the cytoplasm.
- Smallpox led to significant morbidity and mortality before eradication efforts succeeded through vaccination.
Transmission and Symptoms: Person-to-person spread via respiratory droplets, characterized initially by flu-like symptoms and followed by rash formation.
Eradication Triumph: Highlight of global public health achievement, showcasing successful vaccination strategies with lingering implications for future virus eradication efforts.