Researchers discovered how these viruses penetrate the cells, a key step for infection and gene delivery The cell unwillingly supports virus entry and infection by providing lipids that are normally used to repair damaged membranes.
Human adenoviruses also cause small pores in the cell membrane. These pores are too small for the virus to get directly into the cell but are large enough for the cell to recognize them as a danger signal and repair them in a matter of seconds. The adenovirus uses this very repair mechanism to trigger an infection.
Incoming adenovirus stimulates calcium influx and lysosomal exocytosis, a membrane repair mechanism resulting in release of acid sphingomyelinase (ASMase) and degradation of sphingomyelin to ceramide lipids in the plasma membrane.
Ceramide lipids enable the virus to enter the cell more rapidly. The ceramide lipids cause the membrane to bend and endosomes to form. Endosomes are small bubbles of lipids and proteins and they engulf extracellular material, such as nutrients, but also viruses. With the aid of the ceramide lipids, the virus increases the size of the membrane lesions, and can leave the endosome before the endosome becomes a lysosome and degrades the virus.
Thus, adenovirus uses a positive feedback loop between virus uncoating and lipid signaling for efficient membrane penetration.