Cancer Gone Viral: This cancer-causing virus hacked the AIDS epidemic

Cancer Gone Viral: This cancer-causing virus hacked the AIDS epidemic

Dr. Talia Henkle
Dr. Talia Henkle

In 10 seconds? Kaposi’s sarcoma herpesvirus (AKA KSHV or HHV-8) is a virus that usually doesn’t cause illness in healthy people. But it becomes one of the most potent cancer-causing viruses in those who are immunocompromised due to HIV infection.

What’s the story? Herpesviruses, as a family of viruses, are like those weird people that nobody wants to get stuck talking to at a party. Once you're introduced to them, they are pretty much impossible to get rid of, and the best-case scenario is they become a vague or imperceptible annoyance in the background. In this allegory – and as the main character in the current episode of our Cancer Gone Viral series, we meet KSHV, who is like an uncomfortably quiet cousin that grows up to be a serial killer.

Wow… are you sure you get out enough? Why the serial killer analogy? Sorry, I got carried away... What I wanted to say was Kaposi’s sarcoma (AKA KS–the main type of cancer caused by KSHV) was a rare cancer associated with small geographical regions and cultural subgroups until it took center stage during the AIDS epidemic in the 1980s. You see, KSHV infection doesn’t cause any symptoms and is quite rare–with only about 1 in 100,000 people infected in the general US population.

But something happened… right? Right. Somehow, KSHV was able to hop on the coattails of the AIDS epidemic. Before the introduction of combined antiretroviral therapies (cART) to treat HIV immunosuppression in the mid-1990s, KSHV rose to infect about 40% of HIV-infected white men and, although much decreased among younger generations, KSHV rates remain elevated among those with HIV to this day.  Whether KSHV was just able to take advantage of the immunosuppressed conditions caused by HIV infection or whether something about HIV specifically helps promote KSHV infection is not fully understood (particularly because other immunosuppressed populations are susceptible to Kaposi's sarcoma but people with HIV infection still seem to have a higher risk). But co-conspiring or not, HIV and KSHV make a regrettable pair.

What kind of cancer is this exactly? KSHV spreads via saliva and infects the cells that line our blood and lymph vessels (called endothelial cells) and can cause them to turn cancerous. The tumors frequently appear as brown or purple blotches, usually on the legs or face. But the real damage is done when tumors form inside the body damaging vital tissues and organs.

Different manifestations of KS tumors or ‘lesions’. Cesarman E, et al. Nat Rev Dis Primers. 2019; 5(1):9

So how does KSHV cause cancer? KSHV, like all herpesviruses, infects us and then hides inside our cells (this is called a 'latent cycle', where no more viruses are being made, but they still exist inside the cells). Only occasionally and under certain conditions will KSHV start replicating (making more clones of itself) again so that it can infect other cells and jump to other people as well. But to complete its life cycle this way KSHV has developed a slew of tricks to hack our cellular programming, which drive KSHV-infected cells out of control when the immune system is damaged.

For example? Meet LANA (latency-associated nuclear antigen), which is one of KSHV’s tumor-promoting proteins. LANA’s main role is helping KSHV anchor its DNA to our DNA in the cell it infects during its latent cycle–so that if the cell divides (AKA makes a copy of its DNA and splits into two new cells) KSHV can hitch a ride and spread to both daughter cells –ensuring that the infection endures as long as our cells do. But KSHV doesn’t want to take the chance that the cell it infects might die (which would also kill the virus) so LANA also plays a role in keeping our cells alive and promoting them to grow. (It messes with our p53 and pRB-E2F signaling similar to HPV). And under immunosuppressed conditions, LANA’s functions added with the effects of multiple other KSHV proteins can push the cells into overdrive and cause them to make mistakes, such as mutations, and turn cancerous.

How is KS treated? For patients who get KS from being immunosuppressed, the first step is to try to fix the immunosuppression and let our immune systems take care of the cancer itself. For those who have both KSHV and HIV, just starting cART treatment for HIV, which helps restore immune function, can successfully treat up to 80% of patients at an early stage. And for patients who develop KS after receiving an organ transplant, they can be switched to different or less potent immunosuppressive drugs (although that risks transplant rejection). When necessary, other cancer treatments like chemotherapies are used to help treat KS.

KS today – it has traveled

These days, about 90% of KS cases are found in African nations such as Zimbabwe, South Africa, Mozambique, and Botswana–which have limited access to medical resources. In these regions, 5-year survival rates for people with KS are much lower than those seen in high-income nations.

What’s more, many of these people with KS are more impacted by other health factors like malnutrition or other infections, which can negatively affect how well a person can respond to treatments.

Although overdue, luckily, efforts are underway to provide these nations with better access to live-saving approaches for diagnostics and treatments

Dr. Talia Henkle has distilled 2 research papers, saving your 7 hours of reading time

The Science Integrity Check of this 3-min Science Digest was performed by Dr. Jacquelyn Bedsaul.

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