Group V and X secretory phospholipase A2 prevents adenoviral infection in mammalian cells

Abstract

sPLA2 (secretory phospholipase A2) enzymes have been implicated in various biological events, yet their precise physiological functions remain largely unresolved. In the present study we show that group V and X sPLA2s, which are two potent plasma membrane-acting sPLA2s, are capable of preventing host cells from being infected with an adenovirus. Bronchial epithelial cells and lung fibroblasts pre-expressing group V and X sPLA2s showed marked resistance to adenovirus-mediated gene delivery in a manner dependent on their catalytic activity. Although adenovirus particles were insensitive to recombinant group V and X sPLA2s, direct addition of these enzymes to 293A cells suppressed both number and size of adenovirus plaque formation. Group V and X sPLA2s retarded the entry of adenovirus into endosomes. Moreover, adenoviral infection was suppressed by LPC (lysophosphatidylcholine), a membrane-hydrolytic product of these sPLA2s. Thus hydrolysis of the plasma membrane by these sPLA2s may eventually lead to the protection of host cells from adenovirus entry. Given that group V and X sPLA2s are expressed in human airway epithelium and macrophages and that the expression of endogenous group V sPLA2 is upregulated by virus-related stimuli in these cells, our present results raise the possibility that group V and X sPLA2s may play a role in innate immunity against adenoviral infection in the respiratory tract.

Lysis of Human Immunodeficiency Virus Type 1 by a Specific Secreted Human Phospholipase A2

“…This finding contrasts with a previous report showing that addition of a nonmammalian sPLA 2 , derived from bee venom, blocked the entry of HIV-1 by steric inhibition of the chemokine receptor on target cells, in which case catalytic activity was not required (6). Another recombinant sPLA 2 -X derived from bacteria inhibited adenovirus plaque formation through its ability to hydrolyze phospholipids on host cell membranes (15), implying a different mechanism of action with a nonphysiological gene product, unlike the report here.…”

Biology of Secretory Phospholipase A2

“…[23], lung [25], liver, spleen, kidney, and ovary [30], brain [31] Digestion of dietary PLs [23], antibacterial [65], eicosanoid formation, cell contraction, proliferation [30], migration [11] PG > PS >> PC [44] M-type [40] II A Acute phase serum, intestinal mucosa, lacrimal gland cells, prostatic epithelial cells [36] Acute phase protein [1,35], antibacterial [60][61][62][64][65][66], cell proliferation [3,4], migration [5], apoptosis [6], atherogenic [124] PG > PS >> PC [44] M-, N-type [40] HSPG [41] C Pseudogene (human) [18] Testis, pancreas (mouse) [44] N/D PG >> PC [44] Low affinity to M-type [ High molecular weight [20]. Antiviral [78] PG > PC [44] Low affinity to M-type [40] V Heart, eye, pancreas [44], macrophages [99], neutrophils [69], mastocytes [70] Antibacterial [17,65], antiviral [77], atherogenic [137,142], AA release, eicosanoid generation …”

Group X phospholipase A2 is released during sperm acrosome reaction and controls fertility outcome in mice

“…This direct mechanism also fits with our results showing that mGX-induced AR does not require intracellular Ca 2+ ( Figure 5C). Based on the specificity and action of group X sPLA 2 on different cells (43,65), the phospholipid targets of mGX on sperm are likely phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine, especially those enriched in polyunsaturated fatty acids at the sn-2 position. Such phospholipids are present in caudae epididymal sperm and reorganized into microdomains in the sperm head plasma membrane during capacitation (10,11,(66)(67)(68)(69).…”