DNA Viruses 2

• Polyomavirus

  • Small (45 nm). Nonenveloped, heat-stable viruses.
  • Mammals and birds are natural hosts
  • Icosahedral symmetry with 72 capsomeres
• Polyomavirus Family: Polyomaviridae

  Has 6 genera

  • Alpha Polyomavirus
  • Beta Polyomavirus
  • Delta Polyomavirus
  • Epsilon Polyomavirus
  • Gamma Polyomavirus
  • Zeta Polyomavirus
• BK VIRUS (BKV)

  • Named after the initials of the patient in whom the virus was first identified
  • Typically infects the urinary system of immunocompromised individuals
• BK virus Clinical Manifestations 

  • Hemorrhagic Cystitis
  • A condition in which the lining of the bladder becomes inflamed and starts to bleed
  • Symptoms include hematuria, dysuria, feeling a need to urinate often, ad being unable to control the flow of urine
  • Urethral Stenosis
  • Uppermost part of your urethra narrows.
  • Preventing pee from passing out of your body normally
• BK Virus Transmission

  • Majority infected during childhood
  • Transmitted via respiratory droplets, contaminated food & water
• JC VIRUS

  • John Cunningham Virus
  • Infects the brain
  • Affects immunocompromised individuals.
• JC Virus Clinical Manifestations

  • Progressive multifocal leukoencephalopathy or vanishing of the white matter in the brain
• JC Virus Wide Range of Symptoms

  • Depending on location and demyelination
  • Progressive motor and neurological symptoms like
  • Weakness
  • Loss of vision
  • Changes in speech 
  • Clumsiness due to lack of coordination
  • Personality changes
  • Dementia
  • PML - Death / Serious Neurological Disabilities
• JC Virus Transmission

  • Respiratory droplets through the respiratory and gastrointestinal organs
  • Cells can be active or latent like the smallpox
  • Travels through the bloodstream
• JC Virus Diagnosis and Treatment

  • CSF samples (Cerebral Spinal Fluid)
  • Multiple white lesions on Brain MRI
  • No treatment, but we can only slow down by restoring the function of the immune system with Immuno-suppressants
• WHAT IS CANCER?

  • All cancers derive from single cells that have acquired the characteristics of continually dividing in an unrestrained manner and invading surrounding tissues.
  • Cancer cells behave in this abnormal manner because of changes in the DNA sequence of key genes, which are known as cancer genes. Therefore all cancers are genetic diseases 
  • Ex: Human melanoma cell undergoing cell division
  • Worldwide, the WHO international Agency for Research on Cancer estimated that in 2002, 17.8% of human cancers were caused by infection, with 11.9% being caused by one of seven different viruses
• VIRUSES AS THE CAUSE OF CANCER

  • An oncovirus is a virus that can cause cancer. This term originated from studies of acutely transforming retroviruses in the 1950-60s often called oncornaviruses to denote their RNA virus origin. 
  • Refers to any virus with a DNA or RNA genome causing cancer and is synonymous with “tumor virus” or “cancer virus”
  • The vast majority of human and animal viruses do not cause cancer, probably because of long-standing coevolution between the virus and its host.
• HOW VIRUSES CAUSE CANCER

  • The viral agents causing cancer in eukaryotic animals by integrating in host genome
  • A virus associated with malignancies in natural host, experimental animals or cell cultures
  • Viruses which modify proto- oncogene, obligatory host specific, with the ability immortalization, possess genes which stimulate growth and cause cancer. 
• GENERAL FEATURES OF VIRAL CARCINOGENESIS

  • Most are DNA virus (exceptions: some retroviruses and flaviviruses)
  • Influence the cell cycle by
  • Encoding proteins that direct cell cycle progression
  • Integrating near cellular genes that control cell cycle progression
• Tenets of viral carcinogenesis

  • Persistent infections
  • Host immune response
  • Virus infections are far more common than viral cancers
  • Viruses are seldom carcinogenic on their own
  • Mechanisms of action by human cancer viruses
• Persistent infections

  All known human tumor viruses establish persistent infections
• Genetic differences in individuals


  Results in differential susceptibilities
• HOW DO VIRUSES CONTRIBUTE TO CANCER?

  • Studies of tumor viruses revealed that specific genes (called oncogenes) are capable of inducing cell transformation, thereby providing the first insights into the molecular basis of cancer.
  • Integrations that cause activation or inactivation of oncogenes or tumor suppressors (e.g. RNA viruses)
  • Expression of genes that alter key signal transduction pathways
  • Chronic activation of inflammatory responses
• Host immune response

  Persistent viruses must evade the host immune response
• Evasion mechanisms

  • Different viruses has evolved different evasions mechanisms
• Virus infections are far more common than viral cancers
• Viruses are seldom carcinogenic on their own
• Mechanisms of action by human cancer viruses

  • Viral gene is able to subvert cell cycle control
  • Viruses alter the expression of normal cell cycle progression genes
  • Either results in cellular transformation into an oncogenic state
• HISTORY

  • The theory that cancer could be caused by a virus began with the experiments of Oluf Bang and Vilhelm Ellerman in 1908  who first showed that avian erythroblastosis (a form of chicken leukemia) could be transmitted by cell-free extracts. This was subsequently confirmed for solid tumors in chickens in 1910-1911 by Peyton Rous.
  • By the early 1950s it was known that viruses could remove and incorporate genes and genetic material in cells.
• 1964: Anthony Epstein, Bert Achong and Yvonne Barr identify the first human oncovirus from Burkitt lymphoma cells. A herpesvirus, this virus is formally known as human herpesvirus 4 but more commonly called Epstein-Barr Virus or EBV.
• • Tumor viruses possess cell specificity and do not infect other cells
  • EBV infects B cells
  • HTLV infects T cells
  • Retention of viral nucleic acid in a cell
  • Viral genes are always present in the transformed cells 
• • 1980: Human T-lymphotropic virus 1 (HTLV I), the first human retrovirus was discovered by Bernard Poiesz and Robert Gallo at NIH and Mistuaki Yoshida and co workers in Japan.
• 2008: Chang and Moore, now at the University of Pittsburgh Cancer Institute, developed a new method to identify cancer viruses based on computer subtraction of human sequences from a tumor transcriptome, called digital transcriptome subtraction (DTS).
• DNA Viruses

  Small DNA tumor viruses

  • Human Papillomavirus (HPV)

  Herpesvirus (large)

  • Epstein Barr virus (EBV)
  • Kaposi’s Sarcoma Herpesvirus (KSHV)

  Other

  • Hepatitis virus B
• RNA viruses

  Human T-cell Leukemia Virus 1 (HTLV1)

  Human immunodeficiency Virus (HIV)

  Hepatitis virus C
• Papillomavirus

  • Size of about 55nm
  • Icosahedral and nonenveloped 
  • Human Papillomavirus (HPV) is one of the most common STDs.
• Papillomavirus Family: Papillomaviridae

  • Has 5 genera capable of infecting humans
  • Alphapapillomavirus
  • Betapapillomavirus
  • Gammapapillomavirus
  • Mupapillomavirus
  • Nupapillomavirus
• Papillomavirus

  Causes clinical manifestations
• Benign Warts


  • Common skin warts
  • Flat warts
  • Filiform warts
  • Plantar warts
• Respiratory papillomatosis


  Development of small, wart-like growths (papillomas) in the respiratory tract
• Respiratory papillomatosis


  • Voice changes
  • High pitched breath sounds
• Anal and Genital infections


  Cause warts called condylomata acuminata
• Anal and Genital infections


  • Cauliflower-like look
  • Typically painless but can cause itching, burning sensation, and localized pain
• Cancer


  Cervical, anal, oropharyngeal, penile, and vaginal
• Cancer

  • Can develop over 1 or 2 decades