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20.8:

Meccanismi dei tumori indotti da retrovirus

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Biologia Molecolare
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JoVE Core Biologia Molecolare
Mechanisms of Retrovirus-induced Cancers

Lingue

Condividere

Retroviruses are a group of single-stranded RNA viruses with the ability to integrate their genome into the host-cell DNA. Upon infection into a suitable host cell, the retroviral core enters the host-cytoplasm. The core contains the viral-genetic material and viral-enzymes like reverse transcriptase and integrase. Once inside the host-cytoplasm, the core disassembles to release its contents. Then, the viral reverse transcriptase enzyme reverse-transcribes the viral-RNA into single-stranded complementary DNA or cDNA. The cDNA replicates to generate double-stranded DNA that enters the host nucleus along with the viral-integrase enzyme. The integrase enzyme catalyzes the incorporation of the double-stranded viral-DNA, called provirus into the host-DNA. The integration of the provirus into the host genome can activate or transform a normal cell into a cancerous cell via several different mechanisms. Such retroviruses are called cancer-causing or oncogenic viruses. For example, the promoter and enhancer sequences present in the provirus may activate the neighboring host genes and trigger abnormal cell growth. Expression of some viral proteins inside the host cell may also indirectly activate the host genes and result in their aberrant expression. At times, the integrated provirus may contain oncogenes in addition to the normal retroviral genes, which upon expression in the host cell drive tumor formation.

20.8:

Meccanismi dei tumori indotti da retrovirus

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host cell surface, forming new viral particles. When the viral genes or products interfere with host genes that regulate cell growth and progression, it leads to cancer progression.

Acute vs. non-acute retroviruses

Some retroviruses called acute viruses can cause cancer after short latent periods. For example, the Rous sarcoma virus can induce sarcomas in the host within three weeks of infection. In contrast, some non-acute retroviruses only cause cancer after long latent periods. Such non-acute viruses induce cancer in only some of the infected hosts. For example, Rous-associated virus-60 induces lymphomas in only 50% of the infected hosts after five to nine months of infection.

However, additional events and host factors such as immunosuppression, somatic mutations, genetic predisposition, and exposure to carcinogens play an important role in cancer progression upon viral infections.

Suggested Reading

  1. Nisole, Sébastien, and Ali Saïb. "Early Steps of Retrovirus Replicative Cycle." Retrovirology 1 (2004): 9. [Source]
  2. Peter K. Vogt. "Retroviral Oncogenes: A Historical Primer." Nature Reviews Cancer 12, no. 9 (2012): 639-48. [Source]
  3. Liao B. John “Viruses and Human Cancer”. Yale J Biol Med. 2006 Dec; 79(3-4): 115–122. [Source]