Since the 20th century it has been known that some infections play role in the development of certain cancers in animals, more recently however, certain viral, bacterial and parasitic infections have been recognised as risk factors for several types of cancers in humans. Worldwide, around 20% of all cancers are caused by infectious agents. Infectious agents can disrupt the cell cycle, cause chronic inflammation or suppress the host’s immune system, all of which seem to increase the risk of cancer.
Viral infection is usually a very active process, where the infected cell is modified. One of the major impacts of viral modification is cell transformation and malignant changes.
1. Retroviruses and Cancer:
During retrovirus multiplication cycle, the virus RNA (positive strand) is first converted into DNA, by reverse transcriptase and the DNA copy is integrated into the host genome. However sometimes a viral promoter may be incorporated close to a host proto-oncogene, for example c-myc, and this may leads to over-expression of that oncogene, in this case it causes chicken leukaemia. Instead, the virus may carry an oncogene itself and during its replication, the virus expresses them at high levels, for example Rous Sarcoma Virus (RSV) which causes Rous sarcoma in chicken due to insertion and over-expression of Src oncogene, an intracellular signalling protein, tyrosine kinase. Also, the virus can acquire host genes, an oncogene in this case, by recombination, and express it at high levels, this is also evident with RSV. Oncogene over-expression leads to increased proliferation and hence increased probability of mutations and hence tumour development. Below are examples of the role of specific retroviruses in certain types of cancers.
i. HBV and Hepato-cellular Cancer (HCC)
Hepatitis B Virus (HBV), a Hepadnaviridae, infects hepatic tissue and causes chronic liver disease, which lead to cirrhosis and hence, HCC. HBV-induced HHC can occur parallel to or without liver cirrhosis, Woodchucks and ground squirrels chronically infected by the woodchuck hepatitis virus and ground squirrel hepatitis virus, respectively, develop HCC against a background of HBV-Chronic Active Hepatitis without cirrhosis; this observation emphasizes the absence of a strict requirement for cirrhosis in liver carcinogenesis.
There are two major ways in which HBV can cause HCC; Firstly, expression of the viral proteins can stimulate the host immune response and trigger liver inflammation, secondly, some viral proteins as well as insertion of the viral DNA into liver cell genome directly interfere with cell proliferation and viability and induce genetic alterations. HBV protein, HBx, which enhances viral replication, is found in higher levels with patients with HCC than those with chronic HepB without cancer. It has been found that HBx sensitizes the hepatocytes to chemical carcinogen by altering oncogenes, such as c-myc. Not only that but it also increased the expression of pro-angiogenic factors, therefore facilitates tumour formation and growth.
About 30% of liver cancers are linked to HBV.
ii. HTLV-1 and Adult T-cell Leukaemia (ATL)
Human T-cell Leukaemia Virus Type-1 (HTLV-1) has been linked with adult T-cell leukaemia (ATL). One of HTLV proteins, tax protein, is crucial for viral replication and for initiating malignant transformation leading to the development of ATL. Tax has been shown to be oncogenic, since it transforms and immortalizes rodent fibroblasts and human T-lymphocytes, by activating genes which are important in spindle assembly checkpoint.
2. DNA-Viruses and Cancer:
i. HPV and Cervical Cancer
Human Papilloma-virus (HPV), a Papovaviridae, is a double stranded-DNA virus and is usually linked to cervical cancer, a sexually transmitted disease. Studies have shown that HPV DNA is found in 95% of all cervical cancers, HPV-16 most prevalent (40-50%) and then HPV-18 (10-30%). HPV 16 and 18…