The occurring of Cancer depends upon multiple factors, and some of this can be caused by viruses like Epstein-Barr Virus, Hepatitis B Virus, Human papilloma virus, and Kaposi’s Sarcoma-Associated Herpesvirus cause a wide range of cancers such as nasopharyngeal carcinoma, Burkitt’s lymphoma, head and neck cancer, and cervical cancer in the host.

WHAT IS HCMV?

Among the viruses a DNA virus known as Human cytomegalovirus (HCMV) is found to be associated with cancer by infection directly or indirectly. However, the question is that it is not yet found to cause cancer but its components still found in tumor tissue and can be considered as the cause of converting a normal cell into a cancerous cell. HCMV infects 90% of the world’s population have knowing how this causes cancer and stop it will help to stop the progression of various cancers.

DETAILS ABOUT HCMV

Human cytomegalovirus (HCMV) is a beta-herpesvirus that causes lifelong infection in humans. HCMV has a prevalence of 55-100% within the human population, depending on different socioeconomic and geographical factors. Primary HCMV infection is generally asymptomatic in healthy hosts but can cause severe and sometimes fatal disease in immunocompromised individuals and neonates. HCMV is the leading infectious cause of congenital abnormalities in the western world, Affecting 1-2.5% of all live births.

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                      Fig: HCMV replication

HCMV VIRAL REPLICATION

HCMV intrauterine infection and can cause significant

morbidity, including low birth weight, hearing loss, visual impairment, microcephaly, hepatosplenomegaly, and varying degrees of mental retardation.

HCMV also causes serious disease in organ transplant recipients and AIDS patients, either after primary infection or reactivation of latent infection. In immunocompromised individuals, HCMV infection is often controlled by early treatment with antivirals but problems exist, such as toxicity.

HOW TO STOP THIS INFECTION

It is known that virus-infected cells release interferons (I-IFNs) to inhibit cancer spread as infected cells undergo apoptosis (infected cells kill themselves) and stop the infection from spreading. But what is special is HCMV acquire strategies to avoid this apoptotic pathway and lead to uncontrolled cell growth.

A novel role of HCMV deubiquitinase (DUB) in oncogenesis. HCMV-DUB is encoded by a unique long 48 genes (UL48), which is known to inhibit various pro-apoptotic genes and induces expression of anti-apoptotic, in short, the infected cell will not undergo apoptosis. It also has some other roles like signaling pathways, immune signaling, apoptosis, oncogenesis, and developmental pathways.

HCMV-DUB inhibits synthesis of I-IFNs, by deubiquitinating (are proteases that cleave ubiquitin from their target substrates) TRAF-6 and -3, interleukin-1 receptor-associated kinase-1, IRF-7 and inhibit the synthesis of interferons.

Is HCMV Association With Various Cancer Tissues?

The role of the HCMV component is poorly understood, but indirectly it shows the role of HCMV immediate-early proteins (IE1 and IE2) in oncogenesis. molecular mechanism in oncogenesis on this pathway is not known very much and scientist has found this by HCMV-infected cells and extended to transfection lead to increased metabolic activity and cell proliferation by promoting G2 phase of the cell cycle, by more expression of antiapoptotic genes (bcl2, birc3, prkce, survivn) and therefore the infected cell unable to stop cell division and continue to divide. What it is trying to say the differential expression pattern of anti- or pro-apoptotic genes might be associated with stimuli, stimulation duration, or cell type. All this observation was done on human foreskin fibroblasts (HFFs) and can say that HCMV promotes survival of infected cells and show also show carcinogenic properties.

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Fig: Summary of the infection by HCMV and its process by HCMV deubiquitase (pUL48).

The above image shows the HCMV deubiquitinase in inhibiting I-IFN synthesis to promote oncogenesis. HCMV-DUB facilitates deubiquitination of TRAF6, TRAF3, IRAK1, and STING to inhibit I-IFN synthesis, which in turn inhibit the expression of several pro-apoptotic genes and induce the expression of new anti-apoptotic genes

Prevention of Viral induced Cancer: 

  1. Prevent transmission of HCMV viruses.
  2. Strategies aimed at reducing the risk of transmission of HCMV viruses.
  3. Vaccination
  4. Attempted elimination from the body of persistent infections with HCMV oncogenic virus.

CONCLUSION

To find out the result scientist performs HCMV infection HFF cells and HCMV non-infected HFF cells and do MTT assay (is a colorimetric assay for assessing cell metabolic activity). And the HCMV infected cell show high metabolic activity, can be due to uncontrollable growth of cells due to cancer, for conformation find out a gene MKi67 which is a proliferation marker gene. And by flow cytometry, it is found that the cell is in G2 stage. And in the second phase scientist infected HFF cells with tumor causing viruses and HCMV, the tumor causing viruses infected cells die as the infected cause activation of the apoptotic pathway in the cell and it dies whereas, in HCMV infected HFF cells, cells still divide because of expression of anti-apoptotic genes and protect the infected cell and favor cancer progression. Collectively, these results indicate that HCMV infection induces oncogenic properties in non-transformed cells through upregulation of anti-apoptotic genes, resulting in enhanced cell proliferation.

REFERENCES:

https://www.nature.com/articles/cddis2017461#Sec9

https://biotechkhan.wordpress.com/2014/07/29/mechanism-of-oncogenic-viruses-and-prevention/

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