UMD researchers associate for the first time a protein with anti-antibody immunity

The human cytomegalovirus (HCMV) may not be a household name for viruses, but according to Xiaoping Zhu, professor and chair of veterinary medicine at UMD, half of the population moving on campus would probably be carrier. Once contracted, it stays dormant in your body for the rest of your life and can strengthen each time your immune system is severely compromised, giving you flu-like symptoms.

This becomes a serious problem for people who already have a weakened immune system, for example the very young, the elderly, pregnant women, organ transplant recipients or patients with HIV / AIDS. More worryingly, however, HCMV is the leading infectious cause of conbad malformations worldwide, including developmental disorders and deafness. But how can a protein play a major role in the development of conbad anomalies and have the potential to relieve autoimmune disease symptoms such as lupus? In a new article published in Nature CommunicationsZhu and his colleagues help answer this question and discover the mechanisms that will lead to multifaceted prevention and treatment.

HCMV remains asleep in our cells. Then one day, you are stressed, you have too much to do and your immunity decreases, allowing the virus to be reborn. "

Xiaoping Zhu, Professor and Chair of Veterinary Medicine at UMD

This is the case of all strains of herpes virus, such as HCMV, chicken pox and herpes simplex. HCMV may have symptoms similar to the flu virus. But unlike the flu, it persists in your body and your immune system must redouble efforts to fight the virus and control it.

It can also be transmitted by the placenta to the unborn child of a pregnant mother, which not only affects the child's immune system, but can also cause birth defects. "When the mother is infected, the virus spreads from mother to child and can lead to mental disorders, vision loss and deafness.People are aware of this concern related to the Zika virus, for example, but the Zika virus does not not stay in your system as long The HCMV, and it is not present in 50 to 80% of the world's population depending on your place of residence, "said Zhu.

This makes the HCMV study and the mechanisms that contribute to its persistence and transmission a high priority for the medical community, as Zhu's work is funded by the National Institutes of Health (NIH). The immune system has two arms of immunity, at the cellular and antibody levels, to specifically kill insects. The mechanisms of the US11 protein that allow HCMV to avoid white blood cells that kill viruses at the cellular level are well known, but in this latest Zhu publication, his colleagues and he discuss a newly discovered function of the same protein which alters the immunity of the antibodies. . Antibody immunity normally prevents viruses from entering and infecting uninfected cells and marks infected cells to be destroyed by white blood cells. But US11 attacks a specific receptor that not only naturally enhances your immunity, but also directs the protective antibodies from the mother to the fetus. When this receptor is impaired, HCMV can reduce the transmission of these critical antibodies, resulting in vulnerability to all kinds of birth defects and, at the very least, compromising the immunity of the child throughout his lifetime. life.

"This is the first time we discover that this virus, or any other pathogen, has this strategy to destroy this receptor function and reduce the functionality of antibodies," Zhu said. "Antibodies are also used to treat diseases such as AIDS, cancer, and vaccine manufacturing, and this mechanism makes this mechanism less effective, and by understanding this function, we can hope to find ways to block this mechanism. 39; future. "

Beyond the prevention of conbad anomalies and immune system dysfunction, Zhu sees another potential benefit for treating this mechanism in patients with autoimmune diseases. "Humans suffer from many autoimmune diseases and, in these cases, as in the case of lupus, it is our immune response that causes the disease, which is regulated by antibodies," Zhu explains. "In these patients, we seek to reduce autoimmune antibodies, because their overproduction causes damage to our own tissues and cells, joint swelling, and significant pain.As this US11 protein can facilitate the degradation of antibodies and suppress their function, could be used in humans to treat autoimmune diseases and target these antibodies originally indirectly beneficial to patients with immune diseases.

This therapeutic perspective is patented by UMD through the intermediary of Zhu and Xiaoyang Liu, who emphasize the importance of directly translating this basic research into applied results and treatment options, not only for humans, but also for animals infected with similar viruses. "Human and animal health research is interconnected," Zhu said. "Similar knowledge can be used to promote human and animal health, and diseases are transmitted directly from animals to humans and vice versa."

Because humans and animals can benefit from this work in many different ways, the applications of this discovery are widespread. The full document, entitled "Human Cytomegalovirus Eliminates Antibody-mediated Immunity by Endoplasmic Reticulum-Associated FcRn Receptor Degradation," is available at the following address: Nature Communications.