[3] Virus–cell fusions occur during infections of several viruses that are health concerns relevant today.
[5] Proteins that allow viral or cell membranes to overcome barriers to fusion are called fusogens.
There is evidence that ancestral species of mammals may have incorporated these same proteins into their own cells as a result of infection.
[7] In response to certain stimuli, such as low pH or binding to cellular receptors, these fusogens will change conformation.
The conformation change allows the exposure of hydrophobic regions of the fusogens that would normally be hidden internally due to energetically unfavorable interactions with the cytosol or extracellular fluid.
This class of fusogens contains some of the proteins utilized by influenza, HIV, coronaviruses, and Ebola during infection.
These proteins are also trimeric and take part in the insertion of fusion loops into the target membrane.
When activated, all of these fusogens form elongated trimeric structures and bury their fusion peptides into the membrane of the target cell.
The outer leaflets of the two membranes form a hemifusion stalk to minimize energetically unfavorable interactions between hydrophobic phospholipid tails and the environment.
"[5] This first step, also known as priming, encompasses the necessary events that must take place in order for cells to gain the ability to fuse.
Some interleukins prompt monocytes and macrophages to fuse to form foreign-body giant cells as part of a body's immune response.
[5] MMP9 can degrade proteins in the extracellular matrix, which aids in the priming of macrophages for fusion.
However, the molecules that induce fusion-competence in macrophages that are destined to become osteoclasts are different from those that promote formation of foreign-body giant cells.
For instance, transcription factor NFATC1 regulates genes that are specific to osteoclast differentiation.
[5] Zygote formation is a crucial step in sexual reproduction, and it is reliant on the fusion of sperm and egg cells.
This unusual location of phosphatidylserine is an example of membrane restructuring during priming for cell fusion.
[5] Syncytin-1 is a Class I fusogen involved in the fusion of cells to form osteoclasts in humans.
[5] It is first accomplished by the mixing of lipids of the outer layers of the fusing membranes, which forms a hemifusion stalk.
[7] Because they are highly conserved, they perform their task through a similar mechanism to the one used by viral fusogens as previously described.