Apoptosis versus survival of African horse sickness virus serotype 4-infected horse peripheral blood mononuclear cells.

The research investigates the factors which either cause cell death or promote survival in horse cells infected with African horse sickness virus serotype 4 (AHSV4), a virus that causes a highly fatal disease in horses. The study focuses on the role of the immune system and how it responds to this virus.

Investigating Cellular Responses to AHSV4 infection

The study employed transcriptome analysis of RNA sequences to investigate how the African horse sickness virus serotype 4 (AHSV4) infection influences peripheral blood mononuclear cells (PBMC) in horses. This method allowed the researchers to delve deeper into the genetic expressions within cells upon exposure to the virus. The primary focus was on understanding whether the virus induced a natural cell death process known as apoptosis or led to the survival of the infected cells.

Apoptosis as Host Defense Mechanism

Apoptosis is a natural cell death mechanism, and it works as a defense method against viral invasions. The study found that in response to AHSV4, the infected cells were using both intrinsic and perforin/granzyme pathways of apoptosis to self-destruct. This process helped prevent further replication and spread of the virus. Specifically, during in vivo primary and secondary immune responses to an attenuated form of AHSV4, apoptosis was the primary method for eliminating the infected cells in order to curb the progress of the virus.

Role of Trained Innate Immunity

Trained innate immunity helps adapt the immune system to better deal with pathogens that it has encountered before. In this study, this mechanism played a crucial role in overcoming viral interference and led to the elimination of AHSV4-infected cells. The elimination occurred via both the intrinsic and extrinsic apoptosis pathways in response to a virulent form of AHSV4 during in vitro secondary immune responses.

Oxidative Stress and Survival of Infected Cells

Despite these defenses, some infected cells survived, specifically during the primary immune response to a virulent strain of AHSV4. Oxidative stress, in collaboration with IRE1α pro-apoptotic signaling, induced the intrinsic pathway of apoptosis. However, the interference of the virus with the immune system, specifically impairing NK cell responses and delaying immune reactions, together with the antioxidant defense system, allowed AHSV4-infected cells to survive. This survival permitted the virus to replicate unrestrictedly. As a result, a virulent AHSV4 in vitro primary immune response led to the survival of the infected cells, allowing the virus to multiply freely.