Adenosine Receptor Modulates Permissiveness of Baculovirus (Budded Virus) Infection via Regulation of Energy Metabolism in Bombyx mori

Abstract

Although the modulation of host physiology has been interpreted as an essential process supporting baculovirus propagation, the requirement of energy supply for host antivirus reactions could not be ruled out. Our present study showed that metabolic induction upon AcMNPV (budded virus) infection of Bombyx mori stimulated virus clearance and production of the antivirus protein, gloverin. In addition, we demonstrated that adenosine receptor signaling (AdoR) played an important role in regulating such metabolic reprogramming upon baculovirus infection. By using a second lepidopteran model, Spodoptera frugiperda Sf-21 cells, we demonstrated that the glycolytic induction regulated by adenosine signaling was a conservative mechanism modulating the permissiveness of baculovirus infection. Another interesting finding in our present study is that both BmNPV and AcMNPV infection cause metabolic activation, but it appears that BmNPV infection moderates the level of ATP production, which is in contrast to a dramatic increase upon AcMNPV infection. We identified potential AdoR miRNAs induced by BmNPV infection and concluded that BmNPV may attempt to minimize metabolic activation by suppressing adenosine signaling and further decreasing the host's anti-baculovirus response. Our present study shows that activation of energy synthesis by adenosine signaling upon baculovirus infection is a host physiological response that is essential for supporting the innate immune response against infection.

Global Metabolic Profiling of Baculovirus Infection in Silkworm Hemolymph Shows the Importance of Amino-Acid Metabolism

“…Analysis indicated a large decrease in the expression of immune-related and metabolic (energy, carbohydrate, and amino acid) pathways at both the mRNA and protein level. In another recent study, extracellular adenosine signaling was implicated in the modulation of host metabolism and immune response during baculovirus infection of the silkworm [ 35 ]. During non-permissive infection of silkworm cells and larvae with Autographa californica NPV (AcMNPV), a much larger production of ATP, circulation of trehalose, and consumption of glucose was observed than after infection with BmNPV, which was interpreted as a mechanism for activation of the immune response rather than as a sign for the requirement of a large energy supply for baculovirus replication [ 35 ].…”

“…In another recent study, extracellular adenosine signaling was implicated in the modulation of host metabolism and immune response during baculovirus infection of the silkworm [ 35 ]. During non-permissive infection of silkworm cells and larvae with Autographa californica NPV (AcMNPV), a much larger production of ATP, circulation of trehalose, and consumption of glucose was observed than after infection with BmNPV, which was interpreted as a mechanism for activation of the immune response rather than as a sign for the requirement of a large energy supply for baculovirus replication [ 35 ]. It was speculated that BmNPV can prevent adenosine receptor signaling and metabolic activation of the immune response through interference with the miRNA regulatory network in the host cells.…”

“…These results confirm our metabolomics data, implying that BmNPV replication does not require glutaminolysis and glycolysis. Another recent study also found that glycolysis has no effect on the replication of BmNPV in permissive cells using 2-DG as inhibitor [ 35 ]. This phenomenon observed for baculovirus infections is different from that detected in infections of other viruses such as Dengue Virus [ 17 ], HSV-1 (herpes simplex virus 1), and influenza A [ 18 ].…”

Advances in the Arms Race Between Silkworm and Baculovirus

“…The antiviral proteins Bmlipase-1 ( 43 ), BmSP-2 ( 44 ), BmNOX ( 45 ), red fluorescent proteins (RFPs) ( 46 ), Bmtryp ( 47 ), and BmLHA ( 48 ) have been isolated from silkworm larva gut juice, which inhibit BmNPV at an initial infection stage. The activation of energy synthesis by adenosine signaling following baculovirus infection is a physiological response in the silkworm that supports its innate immunity ( 49 ). Melanization is a prominent humoral response in insects.…”

Ac106/107 affects production of infectious progeny BV by regulating transcription of late viral genes and host cell energy metabolism

“…The proliferation of the virus depends on the host, and will provide itself with a favorable proliferation environment by affecting the physiological conditions of the host 15 . Studies have shown that baculovirus infection could affect the oxygen consumption and the activity of tricarboxylic acid (TCA) cycle of host cells 16–18 .…”