Genetics and infection with another virus could explain immune differences

2023-08-11 14:42:58

Not all patients reacted in the same way to Covid-19. According to a study published this Wednesday in the journal Naturea prior infection by another virus, cytomegalovirus, but also the genetic diversity of human populations play a role in the variable immune reactions to the coronavirus.

French scientists (Institut Pasteur, CNRS, Collège de France), supported by international researchers, have studied the variations in immune responses to SARS-CoV-2 depending on the origins. They exposed immune blood cells obtained from 222 healthy donors from Central Africa, Western Europe and East Asia to the virus.

The influence of natural selection

Using single-cell RNA sequencing, they analyzed the SARS-CoV-2 responses of 22 blood cell types and combined these results with serological and genetic information about the same individuals. Scientists have thus identified around 900 genes with different behavior depending on the population. Variations mainly due, according to them, to the cellular composition of the blood. However, among the factors influencing these cellular differences is exposure to cytomegalovirus (infection, generally harmless, of the herpes family). 99% of the population of Central Africa is seropositive for the cytomegalovirus, against 50% of that of East Asia and 32% of Europeans.

A latent cytomegalovirus infection could thus increase the risk of Covid severity. Genetic singularity also plays a role: it controls the expression of around 1,200 genes in the face of Covid, according to the study. Thus, “natural selection has influenced current immune responses to SARS-CoV-2, particularly in people of East Asian descent, where coronaviruses engendered strong selection pressures around 25,000 years ago”, according to Maxime Rotival (Pastor), main co-author with Lluis Quintana-Murci.

The interest of paleogenetics

The study also establishes a link between a part of prehistoric heritage and immune disparities. Between 1.5 and 2% of the genes of Europeans and Asians come from Neanderthals. By comparing some of their results and the genome from Neanderthals, the scientists discovered dozens of genes that affect antiviral mechanisms and result from ancient crosses between Neanderthals and Homo sapiens.

This work is a new illustration of the contributions of genetics to understanding the pandemic. Still in mid-July, a study in Nature showed that people with a certain genetic variant are twice as likely not to get sick when they contract Covid-19. Paleogenetics also confirms its interest. In 2020, two years before his Nobel Prize in medicine, the Swede Svante Pääbo had highlighted, with other researchers, the presence of a particular portion of DNA, inherited from Neanderthal man, in the most ill patients. severe Covid. This portion of DNA is more common in populations from South Asia.