The Link Between Human Evolution and Hepatitis C Virus

As humans evolved, they developed a vulnerability to hepatitis C virus (HCV), but according to new research a small group of humans appears to have avoided the deficit.

That’s the central finding of new research that looked into the evolution of the interferon lambda 4 (IFNL4) in humans. Study co-authors John McLauchlan, PhD, and Connor Bamford, PhD, both of the University of Glasgow, told MD Magazine® IFNL4 doesn’t respond to HCV the way one would expect.

“Typically, you would expect that an interferon gene will act against any virus but in this case, IFNL4 appears to promote the development of chronic infection after an acute phase of infection,” said the investigators.

Thus, in the fight between the immune system and HCV, IFNL4 represents a vulnerability that benefits HCV to the detriment of humans.

However, it wasn’t always that way.

McLauchlan and Bamford found that chimpanzees have a different, more active version of IFNL4 that allows them to better fight off HCV. What’s more, the researchers also found that a very small group of humans—members of hunter-gatherer tribes in Central Africa, known as Pygmies—have a version of IFNL4 that is similar to the chimpanzee variant, making members of these tribes uniquely protected against HCV.

The pair said the findings suggest the change in IFNL4 occurred very early in human evolution.

“This allowed us to become more susceptible to HCV,” McLauchlan and Bamford said. “We don’t think that the evolution of the IFNL4 gene in humans as necessarily driven by exposure to HCV, it is maybe more likely the virus has simply exploited a gap in our immune defense system.”

It’s not clear why a small group of humans has the rare version of IFNL4. 

“We cannot tell whether Pygmies and some Africans retain an ancestral version that has persisted at a low level since humans and chimpanzees diverged or whether they have 're-evolved' it,” McLauchlan and Bamford said. “We think further study of Pygmies and these rare African carriers would help figure out how their immune systems differ compared to non-carriers, which would be a fascinating study.”

Their hypothesis is that environmental factors, including exposure to viruses or bacteria, might account for the variant.

Either way, the new understanding unlocks a number of potential research pathways, though there’s no longer a need to look at IFNL4 as a pathway to cure HCV, since direct-acting antivirals (DAAs) are so effective.

“In the past, interferon-alpha was the mainstay of treatment but is increasingly no longer used because of DAAs,” they said. “So we would not consider IFNL4 as a way of treating those who are HCV-infected.”

However, McLauchlan and Bamford said the findings do give a window into how viruses like HCV can sneak past human defenses.

“In terms of where our research goes from here, we now have the tools to look at other viruses such as HIV or hepatitis B, that are also chronic blood-borne infections and ask questions about whether and how these viruses may also have exploited the gap created by the evolution of IFNL4 in humans,” they said.

They added that researchers should also look more closely at the evolution of IFNL4, its interaction with viruses, and whether or not any other species have the same weak, inactive form of the interferon.

The study, “A polymorphic residue that attenuates the antiviral potential of interferon lambda 4 in hominid lineages,” was published online in PLOS Pathogens.

This article was originally published by MD Magazine.

Stay up to date on the latest news in specialty pharmacy by getting Specialty Pharmacy Times in your mailbox or inbox for free!

Click here to sign up for free for the bi-monthly Specialty Pharmacy Times print journal delivered to your address.

Click here to sign up for our email newsletters delivered every Monday, Wednesday, and Friday, in addition to breaking news alerts.

Click here to follow us on Facebook. 

Click here to follow us on Twitter. 

Click here to join our LinkedIn group. 

Most Popular

Related Articles

Glecaprevir/pibrentasvir (G/P) plus sofosbuvir and ribavirin can potentially treat patients who experienced previous virologic failure following G/P therapy.
HIV infection is associated with higher rates of hepatitis C replication.
An increasing number of patients with decompensated cirrhosis are receiving direct-acting antiviral treatment and attaining sustained virologic response of hepatitis C, however, their long-term outcomes are unclear.
Company Profile >
Industry Guide >
Market News >
Peer Exchange >
Conferences >
Subscribe >
Specialty Times Resources
About Us
Contact Us
Terms & Conditions
MJH Associates >
Pharmacy Times
American Journal of Managed Care
MD Magazine
Targeted Oncology
Physicians' Education Resource
Pharmacy & Healthcare Communications, LLC
2 Clarke Drive
Suite 100
Cranbury, NJ 08512
P: 609-716-7777
F: 609-716-4747

Copyright Specialty Pharmacy Times 2006-2018
Pharmacy & Healthcare Communications, LLC. All Rights Reserved.