microbiology today
Mechanisms of virus action
Broadly speaking there are two mechanisms by which viruses
cause tumours – direct and indirect. The direct mechanism
involves the virus infecting a cell and expressing its own
genes. These gene products then enhance the growth potential
and/or survival of that cell. Next, over time, if other growth
enhancing changes occur in the same cell it may grow into a
cancer, for which the virus would be an essential element but
insufficient on its own.
The indirect mechanism of tumourigenesis involves the
virus acting as a cofactor for the tumour but not actually being
present in the tumour cells. Human immunodeficiency
virus (HIV) is a good example here, since by causing severe
immunosuppression it allows other viruses, such as EBV and
Kaposi’s sarcoma-associated herpesvirus, to act opportunistically
and cause uncontrolled cell growth in the absence of
the normal immune control mechanisms.
Cancer treatment and prevention
The importance of the identification of an association
between viruses and various types of cancer is that it opens
up new possibilities for cancer prevention and treatment.
Because virus-associated cancer cells express viral antigens,
they can be recognized as ‘foreign’ by the immune system. So
vaccines can be developed which induce an effective immune
response to the virus and can thereby prevent infection
and consequent tumour production. Vaccines for HBV
and HPV are at present being tested in clinical trials and are
giving encouraging results. Also, where tumours develop in
the setting of immunosuppression, the key elements of the
immune response controlling the virus infection, cytotoxic T
cells, can be grown in the laboratory and given to patients to
prevent or treat the tumour. With these various strategies,
hopefully it will not be that long before the worldwide
incidence of virus-associated cancers is dramatically reduced.
Dorothy H. Crawford
Professor of Medical Microbiology and Head of School of
Biomedical & Clinical Laboratory Sciences, University of
Edinburgh, Hugh Robson Building, George Square,
Edinburgh EH8 9XD (t 0131 650 3142; f 0131 650 3711;
e
d.crawford@ed.ac.uk)
Table 1. Viruses associated with cancer in humans
Family Virus Benign disease Tumour
Retroviridae Human T-lymphotropic virus 1 Tropical spastic paraparesis Adult T-cell leukaemia/lymphoma
Papillomaviridae Human papillomaviruses Benign warts Cancer of cervix, skin, anus, penis
Hepadnaviridae Hepatitis B virus Hepatitis, cirrhosis Hepatocellular cancer
Flaviviridae Hepatitis C virus Hepatitis, cirrhosis Hepatocellular cancer, lymphoma
Herpesviridae Kaposi’s sarcoma-associated herpesvirus Castleman’s disease Kaposi’s sarcoma, Body cavity
lymphoma
Epstein–Barr virus Infectious mononucleosis Burkitt’s lymphoma, Hodgkin’s
lymphoma, B lymphoproliferative
disease, Nasopharyngeal carcinoma