Papillomaviridae and Polyomaviridae

Latency

Virus remains dormant without reproduction but allows persistence and reactivation

Episomal Latency

• Use genetic episomes in latency to stabilize viral genes

  • Used by papillomas, polyomas, and herpes

Proviral Latency

DNA integration directly into host (HIV)

Papillomavirus

Known for causing warts in mammals and birds

Warts

Can be papilloma or benign epidermal tumors

HPV (Human Papilloma Virus)

Virus that causes warts and high risk of cancer, usually by sexual transmission

Types of Warts

• Common

• Plantar

• Subungual

• Periungual

• Flat

Common

Raised; include genital warts

Plantar

Grow inward on soles of feet

Subungual Warts

Grow under the fingernail

Periungual

Grow under the cuticle

Flat Warts

On arms, face, and forehead; common in children

Lewandowsky-Lutz Dysplasia

Uncontrolled HPV Infection

HPV Virion

• Non-enveloped, icosahedral capsid

• Viral proteins are NOT encapsidated

HPV Genome

dsDNA

HPV Capsid

• Capsomeres of L1 protein

  • 5 copies of L1

Unique Feature of L1 Protein

Can self-assemble into empty capsomeres; important to vaccines

E6 and E7 Genes

HPV Genes that cause cancer by affecting p53 and Rb

Epidermis Structure

Basal cells are actively growing (deepest layer); spinous, granular, and cornified cells differentiate

Which cells of the epidermis does HPV have to infect?

Basal cells since they are actively growing; good for replication

Master Regulator Genes

Transcription factors that regulate genes (regulons) and are not under influence of any other gene

What does cell cycle dysregulation lead to?

It leads to cancer.

p53

Master gene regulator that suppresses tumors by inducing apoptosis, repair, cell cycle arrest

HPV Effect on p53

E6 degrades p53; suppresses apoptosis, cell cycle arrest

pRb

Prevents excessive cell growth by inhibiting cell cycle progression and proliferation

HPV Effect on pRb

E7 degrades pRb; immortalization, instability

Immunological Control

Blocks appearance of symptoms but is type-resistant (resistance to one HPV does not mean resistance to others)

HPV Low Grade Lesion

DNA is present in episomal state; E6 and E7 regulated

HPV High Grade Lesion

DNA in integrated state; E6 and E7 expression increased

Treatment of Warts

Removal

Treatment of Cancer

Standard chemotherapy

Are there antiviral treatments for HPV?

No, antiviral treatments are not effective.

Cancers caused by HPV

• Cervical (detected by pap smear)

• Throat cancer (new; more prominent in older men)

  • Symptoms don’t appear until advanced

Polyomaviruses Differences to Papillomaviruses

1. Not epidermal

2. Life cycle not linked to differentiation

3. Tropism varies

4. Outcome varies

Examples of Polyomaviruses

JC (CNS) and BK (KIDNEY)

Polyomavirus Structure

Non-enveloped, icosahedral

Polyomavirus genome

One copy of dsDNA

Spread of Polyomaviruses

1. Inoculation and replication in respiratory tract

2. Viremia

3. Multiply in kidney

4. Secondary viremia

5. Reactivation (CNS in JC or Kidney in BK)

JC Virus Infection

Initial site of tonsils, tubular epithelial cells, can cross BBB

JC Virus Outcomes

• Lyses infected cells in brains of immunocompromised

• Demyelination

• Multifocal leukoencephalopathy

BK Virus Infection

• Primary in childhood; mild and asymptomatic

  • Through urine or respiratory

• Enters bloodstream, mononuclear cells

• Latent in kidney

BK Outcomes

• Inflammation and nephropathy

  • Problem for transplant patients

• Hemorrhagic cystitis

Virobiota

Stable members of human microbiome; evolutionary advantage to good bacteria; protect mucosa