lecture 3: Papillomaviridae Polyomaviridae

latency

Virus remains dormant in the host cell, not producing viral particles but can reactivate later (example: herpes cold sores)

episome

a genetic element that can replicate independently of the host chromosome or integrate into it

Episomal Latency

Viral genome stays as an episome (not integrated), circular / linear / lariat, transcriptionally silent (repressed)

NOT integrated, dormant DNA

Episomal Latency viruses

Used by papillomaviruses, polyomaviruses, herpesviruses

Proviral Latency

DNA integrates directly into the host cell genome (HIV)

Papillomavirus

infects mammals and birds, was discovered from filtered wart material and is transmitted by skin to skin

warts

benign epidermal tumors

HPV (Human Papilloma Virus)

Most common viral STI that causes warts and some strains cause cancer

HPV prevention

vaccine available that prevents infection and cancer

Common warts

hands, feet, elbows; cauliflower-like; non-cancerous

Plantar warts

soles; grow inward → painful; black dots = clotted vessels

Subungual

under fingernail; hard to treat

Periungual

under cuticle; hard to treat

Flat warts

face, arms; common in kids/teens; non-cancerous

Oral lesions & genital warts

caused by specific HPV strains

HPV virion structure

Non-enveloped, icosahedral capsid, circular dsDNA genome that carries NO viral proteins (VERY unusual).

No polymerase, no integrase—just DNA

HPV capsid

L1 protein alone will self-assemble into empty capsids of this form – this is the basis for the HPV vaccines

HPV genome

small, contains L1/L2 capsid proteins, E1/E2 for replication and transcription factors, and E6/E7 is oncogenic

oncogenic

can cause cancer by disrupting host cell regulation, leading to uncontrolled growth

HPV E6/E7

involved in immortalization & escape from cell cycle arrest & apoptosis….. CANCER

blocks p53 and blocks Rb

epidermis

consists of layers with cornified, granular, spinous, and then basal layer

HPV infects only

the cells of the basal cells by breaking through the skin to reach basal layer

HPV Life Cycle

Early genes: E1, E2, E6, E7 expressed first

Late genes: genome amplification + capsid proteins

Virions released when superficial layers shed

Integration of cancer

HPV DNA integrates and only E6 & E7 overexpressed; all other viral genes shut down.

p53 and Rb (retinoblastoma protein)

master gene regulators that prevent cancer transcription factors by controlling cell cycle, DNA repair, apoptosis, its essential for preventing uncontrolled growth

Cancer cells:

Dysregulation, uncontrolled division, abnormal nuclei, loss of boundaries, and loss of contact inhibition

How HPV Causes Cancer: E6

p53 stops cell cycle, repairs DNA or triggers apoptosis but this viral protein sends p53 proteasome degradation which allows cells with DNA damage to survive causing cancer

How HPV Causes Cancer E7

targets Rb for degradation causing uncontrolled proliferation and Rb blocks excessive cell cycle progression

Low Grade Lesions

Episomal HPV DNA and E6/E7 expression regulated

High Grade Lesions

Integrated DNA and high E6/E7 expression across layers

HPV Vaccines

prevents infection and cancer using L1 proteins self assembly

no antiviral drugs

antiviral treatment

none b/c only one viralenzyme

HPV types of cancers

Vaginal, anal, cervical, vulvar, penile, oropharyngeal cancers

pap smear used

Polyomaviruses: JC, BK

Not epidermal, life cycle is not linked to differentiation, cell tropism varies, and disease outcome varies

Polyomavirus Structure

small non-enveloped, icosahedral capsid, and circular dsDNA (supercoiled)

JC and BK spread on body (not immunodeficient)

1.Enter respiratory tract

2.Replicate

3.Primary viremia

4.Spread to kidney

5.Secondary viremia

6.Latency in kidney (if immunocompetent)

BK immunodeficient

urinary tract (kidney/bladder) → hemorrhagic cystitis

viruria, cystitis

JC immunodeficient

central nervous system → progressive multifocal leukoencephalopathy (PML)

fatal; demyelinating disease

John Cunningham virus (JC)

human polyomavirus, effects 70-90% of people, and infected tonsils or tubular epithelium of kidneys

-crosses blood brain barrier

JC replication cycle

after viremia it crosses the BBB where it infects oligodendrocytes/astrocytes which causes PML, it enters via clathrin-mediated endocytosis and released by lysis (non-enveloped)

JC pathogenesis

latent in kidney/bone marrow, transported to brain inside B cells which causes demyelination, weakness, and poor coordination

BK virus

discovered in renal transplant patients, most infection occur in childhood, mild or asymptomatic, persist in kidney cells for life

BK replication

infects respiratory tract, then infects blood (viremia), hides in B cells/T cells/ monocytes, uses caveolin independent endocytosis and released by lysis (no integration)

BK disease

reactivation in immunocompromised patients, causes hemorrhagic cystitis, painful urination, incontinence, and a balance b/t immunosuppression is needed (too much is bad, too little is bad)

nephropathy

in transplant patients BK causes

Commensal viruses

are common, inapparent infections that do not usually cause symptoms or disease in the host

virobiota

the vast community of viruses (bacteriophages, eukaryotic viruses, retroviruses, giant viruses) living in and on the human body