Continued from Part 1

  1. DNA Viruses

  1. Epstein Barr Virus (EBV)
  • First human tumour causing virus to be discovered
  • Belongs to class Human Herpes Virus 4
  • 2 modes of infection – Lytic, Latent cycle
  • Causes Burkitt’s lymphoma – aggressive, malignant cancer characterized by a solid tumour composed of aberrant B-cells
  • Hits teens and young adults by causing infectious mononucleosis
  • Passed through saliva of an infected person, hence called kissing disease, sharing glass, utensils or straw
  • Incubation period – 4-7 weeks
  • Initial signs – sore throat, tonsillitis, fatigue, anorexia, headache, white patches in the back of throat
  • Mononucleosis – enlarged spleen, may even rupture
  • Burkitt’s lymphoma occurs when a person is immunocompromised with AIDS or chronic malaria. EBV persistently infects B cells causing latent infection. Affects jaws, rapidly spreads to soft tissues and parotid glands. Involves chromosomal translocation between chromosome 8 (invariably) and 14, rarely with chromosome 2 or 12. This moves c-myc oncogene on chromosome 8 downstream of immunoglobulin heavy chain gene on chromosome 14 resulting in abnormal expression of the oncogene.
  • Named after Anthony Epstein and Yvonne Barr who first isolated the virus

 

  1. Kaposi’s Sarcoma
  • 1st described by Moritz Kaposi in 1872
  • Occurs in elderly men with an incidence ratio of 10-15 men:1 women
  • Average age of onset – 50-70 years in men of Mediterranean, Middle Eastern or Eastern European ethnic descent
  • Single or multiple lesions in lower extremities – ankles, soles
  • 1981 – 1st reported as a part of AIDS in young homosexuals & bisexuals
  • Poses problems in patients under HAART (Highly Active Anti-Retroviral Therapy) and transplant patients undergoing immunosuppressive drugs
  • Belongs to class Human Herpes virus 8
  • Viral DNA sequence is detected by PCR in biopsy material from patients
  • <3% cells show lytic infection. mRNA transcripts of latent viral genes found in most infected host cells
  • Encodes D-type cyclin, IL-6 homolog, Bcl 2 homolog etc. that help in transformation of human cells

 

  1. Hepatitis B & C Virus (HBV, HCV)
  • Cause chronic hepatitis that could lead to liver cirrhosis and hepatocellular carcinoma (HCC)
  • HBV – ds-DNA genome
  • HCV – RNA genome, replicates in cell cytoplasm
  • Both infect hepatocytes, HCV also infects B-cells
  • In HCC, in tumours caused by HBV, integrated viral DNA is seen whereas in case of HCV , having an RNA genome does not contain an obvious oncogene & no integration is seen
  • HCV causes chromosome instability. Rises mutation by 5-10 fold in certain genes – Ig H chains, bcl-6, p53, β-catenins
  • Transmission – entry via blood or body fluids into non-immunized persons, infected needles, infected mother to baby during birth
  • HBV can also be sexually transmitted
  • Rate of progression from chronic hepatitis to cirrhosis to cancer is higher for HCV than HBV
  • HCC – not detected until an advanced stage. Hence, liver cancer is usually fatal within a year of diagnosis
  • 5th most common cancer in the world
  • Hepatitis B vaccine has lowered the incidence rate. No vaccine for HCV is available as of now
  • Donated blood is screened for
    • HBV & HCV – US, Canada
    • HBV – South East Asia

 

  1. Human Papilloma Virus
  • Common among sexually active adults and adolescents
  • One of the most prevalent STD of the world today
  • Causes cervical cancer which becomes the major cause of death among women in developing countries and is the 2nd most common cancer among women in the world
  • PAP screening programs have reduced cervical cancer mortalities
  • 118 types of virus discovered. Common host is humans. Also found in other mammals & birds
  • Cause benign papillomas or warts in skin of hands and soles, genitals or mucus membrane
  • 3 categories :
    • High risk types – cancer of cervix, vulva, vagina, anus, penis (eg., Type 16 & 18). 4-20 years latent period of infection
    • Low risk types – benign tumours (eg., Types 6 & 11)
    • Intermediate type – HPVs are frequently found in pre-cancerous lesions, less often cause cancers (eg., Types 31, 33, 51, 52, 83)
  • Structure Of Virus
    • Small, non-enveloped, icosahedral, ds-circular DNA virus, 52-55nm diameter, 8000bp
    • Can infect only multiplying basal epithelium cells which are metabolically active
    • Enter through cuts and abrassions
    • Replication and virion assembly occurs in nucleus

Some Useful Information

  • Bivalent vaccine for HPV is available that is 100% effective against persistent HPV – 16 & 18 infections. Reduces incidences of cervical cancer.
  • Vaccine preparation – HPV 16 & 18 L1 genes expressed in S.cerevisiae cells in high quantities. The proteins self-assemble to give a virus – like particle (VLP) without the genome. It infects human epithelial cells of cervix and causes papillomas. Injected intramuscularly into arms.
  • This vaccine is 62% efficient in females and 64% in males
  • GARDASIL – Manufactured by Merck and licensed by FDA in 2006. CDC recommends 11-12 aged females to get vaccinated in order to reduce cases of cervical cancer. Several states are mandating the use of this vaccine.

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