Research Shows Activation-Induced Cytidine Deaminase (AID) And APOBEC Proteins Play A Important Role In The Human Immune System Against The SARS-CoV-2 Virus
A new study by researchers from the Medical University of Vienna-Austria, Nebion-Switzerland and the National Institutes of Health-United States has shown that together with their multifaceted action mechanisms, activation-induced cytidine deaminase (AID) and so-called APOBEC proteins are important factors in the body's immune response and offer fast and effective protection against a large number of DNA and RNA viruses including the SARS-CoV-2 coronavirus.
In the study abstract, the authors said, “The AID (activation-induced cytidine deaminase)/APOBEC (apolipoprotein B mRNA editing enzyme catalytic subunit) family with its multifaceted mode of action emerges as potent intrinsic host antiviral system that acts against a variety of DNA and RNA viruses including coronaviruses. All family members are cytosine-to-uracil deaminases that either have a profound role in driving a strong and specific humoral immune response (AID) or restricting the virus itself by a plethora of mechanisms (APOBECs). In this article, we highlight some of the key aspects apparently linking the AID/APOBECs and SARS-CoV-2. Among those is our discovery that APOBEC4 shows high expression in cell types and anatomical parts targeted by SARS-CoV-2. Additional focus is given by us to the lymphoid structures and AID as the master regulator of germinal center reactions, which result in antibody production by plasma and memory B cells. We propose the dissection of the AID/APOBECs gene signature towards decisive determinants of the patient-specific and/or the patient group-specific antiviral response. Finally, the patient-specific mapping of the AID/APOBEC polymorphisms should be considered in the light of COVID-19.”
The study findings were published in the peer reviewed journal: Frontiers In Immunology.
The main task of AID is to strengthen the human immune response, while APOBECs are able to block the virus.
The study team comprising mainly of Dr Anastasia Meshcheryakova, Dr Diana Mechtcheriakova and Dr Peter Pietschmann from the Institute of Pathophysiology and Allergy Research at Medical University of Vienna has now addressed the potential interrelations between AID/APOBECs and the SARS-CoV-2 virus, particularly in connection with the course of COVID-19 in different patients.
These study findings could provide a starting point for future clinical strategies to improve and strengthen individual antiviral response.
The detailed defense mechanisms associated with AID/APOBECs in response to the coronavirus were assessed on the basis of integrative data mining and gene expression analyses, as part of a study conducted with international partners. It was found that members of the APOBEC family are preferentially expressed in a particular type of cell or tissue.
Dr Mechtcheriakova told Thailand Medical
News, “However, this does not mean that a particular cell type only
expresses a particular member of the APOBEC family but that each cell type exhibits its own characteristic APOBEC repertoire."
However what is c
ompletely new and interesting is that the study team found that APOBEC4 is highly expressed in cells and tissues that are points of attack for SARS-CoV-2. These include epithelial cells in the bronchi, in the lungs, in the trachea and in the nose. It was also found that there is an extremely high level of expression of both molecules (one of the members of the APOBEC family and ACE2, the entry receptor for SARS-CoV-2), in the gastrointestinal tract, in the heart and in the testis.
Dr Mechtcheriakova explained, "Based on this knowledge, the clinical challenge in the future will be to characterize the antiviral cell status attributed to AID/APOBECs specific to patients and/or patient groups and to correlate the cell-type-specific AID/APOBEC gene expression signature with the organs affected by SARS-CoV-2 infection and the severity of COVID-19.”
Importantly a particular role in this process is attributed to AID, since it co-determines the strength of an adaptive immune response.
Dr Anastasia Meshcheryakova further explained, "The AID-driven, highly coordinated sequence of events, which all occur in specialized immunological lymphoid structures with germinal centers, results in the production of high-affinity antibodies by plasma cells or memory B cells. These antibodies are directed against the pathogen causing the disease, such as SARS-CoV-2, either in the course of infection or of an immune response to a vaccine."
The study team stressed that the role of these complex lymphoid structures and of AID is of great importance for the further understanding of the pathobiology of COVID-19, and consequently for the development of new therapeutic approaches.
For the latest on COVID-19-Immunology
, keep on logging to Thailand Medical News.