The professor of Immunology at the Complutense University of Madrid (UCM), Dr. Narcisa Martínez Quiles, maintains that the different severity of hantavirus among patients is due, "to a large extent," to "a matter of genetic lottery."
"Why do some people only present a milder infection while others end up in intensive care with massive fluid leakage in their lungs?" asks the specialist, to emphasize that "the answer" lies in "one's own DNA," and more specifically "in the genetic factors that control the immune response: immunogenetics."
The researcher, author of a popular science article for the Office of Transfer of Research Results (OTRI) of the UCM's Unit of Scientific Culture and Innovation, highlights that "one of the main protagonists" in how the body deals with an infection "is the human leukocyte antigen (HLA) system."
This system "is responsible for showing our immune cells selected fragments of the virus," but, as she recalls, "not all human beings have the same system: there are many different genetic variants (alleles) of these HLA genes, and some appear to influence the severity of the disease." In this context, she points out that "certain of these variants, such as the HLA-B08 allele, act as a 'nudge' towards severe disease after infection with Puumala hantavirus, causing an exaggerated inflammatory response" that ends up damaging one's own tissues.
At the same time, she points out that "conversely, lucky carriers of the HLA-B27 allele tend to experience a much milder and more controlled clinical course, although the interpretation of these types of studies is not so simple." She adds that "before the HLA system comes into play, a silent battle is fought in our cells involving the production of interferons, defensive proteins that are blocked by the Andes hantavirus, the one responsible for the outbreak on the cruise ship 'MV Hondius'."
Along these lines, she warns that "if, in addition to this sabotage, the infected person has less suitable variations (elevated or decreased production) in the genes that must respond to this alarm (such as the Mx1 gene, responsible for manufacturing a key protein to slow down viral replication), the pathogen gains a devastating advantage from the first minute."
CYTOKINE STORM
"When the immune system reacts to the massive invasion, it panics and the so-called 'cytokine storm' is unleashed, in which large amounts of inflammatory substances are released uncontrollably," continues Martínez Quiles. He specifies that "small variations in the genetic code of the genes that encode these cytokines, their receptors or mediators - such as tumor necrosis factor (TNF) - determine whether this inflammation will be beneficial or destructive."
Likewise, he explains that "in the most severe patients, this hyperactivation causes the walls of the blood vessels to lose their impermeability, causing the dreaded hemorrhages and 'capillary leak' that floods the lungs or collapses the kidneys."
To conclude, after alluding to hantavirus mutations, which can occur in one of its segments and which "could facilitate or hinder the entry of the virus," he emphasizes that "surviving a hantavirus does not depend solely on the aggressiveness of the intruder, but on the genetic architecture of the host that receives it."