the progeny virus particle formation; this is done through the promotion of nuclear export of iav formed viral ribonucleoproteins from the nucleus to the cytoplasm. experimentation has also demonstrated that if binding is inhibited between sulfatide and hemagglutinin that viral particle formation and replication would be inhibited, again suggesting that the binding between sulfatide and hemagglutinin facilitates iav replication. vaccinia virus vaccinia virus is closely related to variola virus, which is known to cause the smallpox disease. the vaccinia virus has been shown to be able to bind to sulfatide through the l5 and a27 membrane proteins on the virus. it has been demonstrated in mouse models that sulfatide prevents the attachment of vaccinia virus to the cell's surface, while also preventing death in mouse models that are typically lethal. this suggests that sulfatide may be one receptor for the vaccinia virus. bacterial infection sulfatide binds to many bacteria, including: enterotoxigenic escherichia coli top10 strain campylobacter jejuni mycoplasma hyopneumoniae haemophilus influenzae actinobacillus pleuropneumoniae helicobacter pylori moraxella catarrhalis bordetella pertussis 987p-fimbriated enterotoxigenic escherichia coli lactobacillus reuteri (jcm1081 and tm105 strains) mycoplasma hominis mycoplasma pneumoniae pseudomonas aeruginosa haemophilus ducreyi sulfatide acts as a glycolipid receptor that functions to aid in the adherence of these bacteria to the mucosal surface. mycoplasma hyopneumoniae and actinobacillus pleuropneumoniae are pathogens that cause respiratory disease in swine. haemophilus influenzae, bordetella pertussis, mycoplasma pneumoniae, moraxella catarrhalis, and pseudomonas aeruginosa cause respiratory disease in humans. accordingly, sulfatide is located in the tracheas of both human and swine, and through the use of sulfatide present in the trachea, these several bacteria are capable of adherence to the respiratory tract. hsp-70 on the outside of h. influenzae, has also been shown to aid in the ability of this bacteria to bind to sulfatide. helicobacter pylori, enterotoxigenic e. coli top10 strain, 987p-fimbriated enterotoxigenic e. coli (a strain of e. coli), and lactobacillus reuteri are different strains of bacteria that are found to adhere to the gastrointestinal tract’s mucosal surface. here, sulfatide is present within the tract and is loaded from outside the tract, aiding the bacteria in adherence to the mucosa. stb is an enterotoxin type b that is heat stable; additionally, it is secreted by the enterotoxigenic e. coli strain, and it causes diarrhoeal diseases in humans and many other species of animals. stb also binds strongly to sulfatide as demonstrated by its binding to sulfatide present on the mucosal surface of a pig's jejunum. additional experimentation suggests that sulfatide is a functional stb receptor. sulfatide may also play a role in mycobacterium tuberculosis, which is the agent that causes tuberculosis in humans. experimentation suggests that sulfatide may be involved in mycobacterium tuberculosis infection, and it may be an element of the cell wall of the bacterium mycobacterium tuberculosis. clinical significance role in alzheimer's disease main article: alzheimer's disease in alzheimer's disease, sulfatide in the brain tissue decreases tremendously, starting in the early stages of the disease. in the mild stages of alzheimer's disease, the loss of sulfatide can be up to 50% in the white matter and up to 90% in the gray matter in the brain. sulfatide concentration in the cerebral spinal fluid is also lower in subjects with alzheimer's disease. the characteristic loss of neuronal function associated with alzheimer's disease occurs via the loss of neurons and synapses, and the deficit is lipid class specific to sulfatides. when comparing sulfatide depletion to other neurodegenerative diseases, alzheimer's disease is the only case in which sulfatide is so dramatically depleted; in dementia no marked sulfatide depletion is observed, while in parkinson's disease, sulfatide levels are dramatically elevated, and multiple sclerosis patients only have a moderate sulfatide depletion. additionally, the loss of sulfatide has been observed to only occur at the very beginning of the disease while at more severe stages, minimal additional sulfatide loss occurs. apolipoprotein e sulfatides in brain tissue has been studied by looking at apolipoprotein e (apoe), specifically the ε4 allele. the ε4 allele of apolipoprotein e is the only known genetic risk factor to significantly indicate late onset alzheimer's disease. possessing the apoe ε4 allele has been associated with a higher risk of developing alzheimer's disease. apoe is a protein that is involved in the transport of many lipids, including cholesterol, and thus, regulates how much sulfatide is in the central nervous system and mediates the homeostasis of the system. it has been found that higher levels of apoe are positively correlated with greater sulfatide depletion. apoe-associated proteins take sulfatide from the myelin sheath and then degrade sulfatide into various compounds, such as sulfate. when apoe is increased, the amount of sulfatide that is taken from the myelin sheath is also increased; hence, there is more sulfatide depletion. sulfatide is also involved in the clearance of amyloid-β peptide. amyloid-β peptides are one of the hallmarks of alzheimer's disease. when they are not degraded properly, these peptides accumulate and create plaques, which are clumps of amyloid-β peptide pieces, and they are highly associated with alzheimer's disease. amyloid-β peptide clearance is important so that this accumulation does not occur. sulfatide facilitates amyloid-β peptide removal through an endocytotic pathway, so when there are high levels of sulfatide, there are lower amounts of amyloid-β peptides. since subjects with alzheimer's disease have lower sulfatide levels, the clearance of amyloid-β peptides is lower, which allows the peptides to accumulate and create plaques in the brain. relationship to vitamin k vitamin k has been found to be associated with sulfatide. not only in animals, but also in bacteria, vitamin k has been observed to influence sulfatide concentrations in the brain. vitamin k in the nervous system is responsible for the activation of enzymes that are essential for the biosynthesis of brain phospholipids, such as sulfatide. when warfarin, a vitamin k antagonist, is added to an animal model system, sulfatide synthesis is impaired. however, when vitamin k is added back into the system, sulfatide synthesis proceeds normally, suggesting that vitamin k is necessary for sulfatide synthesis.