Human group III phospholipase A2 suppresses adenovirus infection into host cells

Mitsuishi, Michiko; Masuda, Shiro; Kudo, Ichiro; Murakami, Makoto

doi:10.1016/j.bbalip.2007.09.006

Cited by 29 publications

(15 citation statements)

References 39 publications

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“…There is more and more evidence suggesting that a subset of human sPLA 2 s contribute to host defense against various types of pathogens, including bacteria (13,16,18,20,51) and viruses (52)(53)(54). We show here for the first time that up to four human sPLA 2 s can inhibit the in vitro growth of P. falciparum, which raises the question of their possible in vivo contribution to host defense against infection by this parasite.…”

Section: Discussionmentioning

confidence: 76%

In Vitro Anti-Plasmodium falciparum Properties of the Full Set of Human Secreted Phospholipases A ₂

et al. 2015

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We have previously shown that secreted phospholipases A 2 (sPLA 2 s) from animal venoms inhibit the in vitro development of Plasmodium falciparum, the agent of malaria. In addition, the inflammatory-type human group IIA (hGIIA) sPLA 2 circulates at high levels in the serum of malaria patients. However, the role of the different human sPLA 2 s in host defense against P. falciparum has not been investigated. We show here that 4 out of 10 human sPLA 2 s, namely, hGX, hGIIF, hGIII, and hGV, exhibit potent in vitro anti-Plasmodium properties with half-maximal inhibitory concentrations (IC 50 s) of 2.9 ؎ 2.4, 10.7 ؎ 2.1, 16.5 ؎ 9.7, and 94.2 ؎ 41.9 nM, respectively. Other human sPLA2s, including hGIIA, are inactive. The inhibition is dependent on sPLA 2 catalytic activity and primarily due to hydrolysis of plasma lipoproteins from the parasite culture. Accordingly, purified lipoproteins that have been prehydrolyzed by hGX, hGIIF, hGIII, and hGV are more toxic to P. falciparum than native lipoproteins. However, the total enzymatic activities of human sPLA 2 s on purified lipoproteins or plasma did not reflect their inhibitory activities on P. falciparum. For instance, hGIIF is 9-fold more toxic than hGV but releases a lower quantity of nonesterified fatty acids (NEFAs). Lipidomic analyses of released NEFAs from lipoproteins demonstrate that sPLA 2 s with anti-Plasmodium properties are those that release polyunsaturated fatty acids (PUFAs), with hGIIF being the most selective enzyme. NEFAs purified from lipoproteins hydrolyzed by hGIIF were more potent at inhibiting P. falciparum than those from hGV, and PUFA-enriched liposomes hydrolyzed by sPLA 2 s were highly toxic, demonstrating the critical role of PUFAs. The selectivity of sPLA 2 s toward lowand high-density (LDL and HDL, respectively) lipoproteins and their ability to directly attack parasitized erythrocytes further explain their anti-Plasmodium activity. Together, our findings indicate that 4 human sPLA 2 s are active against P. falciparum in vitro and pave the way to future investigations on their in vivo contribution in malaria pathophysiology.

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Section: Discussionmentioning

confidence: 76%

In Vitro Anti-Plasmodium falciparum Properties of the Full Set of Human Secreted Phospholipases A ₂

et al. 2015

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“…GIII, GV and GX sPLA 2 s are capable of preventing host cells from being infected with adenovirus. 63 The antivirus activity of GV and GX sPLA 2 s is due to the enzyme activity which converts PC to lysoPC in the host cell membranes. This hydrolysis of the cell membrane protects the host cells from adenovirus entry.…”

Section: Secreted Phospholipase A2 (Spla2 Groups I Ii Iii V Ixmentioning

confidence: 99%

“…This hydrolysis of the cell membrane protects the host cells from adenovirus entry. 63a GIII sPLA 2 has a different antivirus mechanism, which requires the presence of both the catalytic domain and the N-terminal domain for the anti-adenovirus effect. 63b By degrading the virus membrane and recognizing the virus envelop, human GX sPLA 2 is capable of neutralizing HIV-1.…”

Section: Secreted Phospholipase A2 (Spla2 Groups I Ii Iii V Ixmentioning

confidence: 99%

“…63a GIII sPLA 2 has a different antivirus mechanism, which requires the presence of both the catalytic domain and the N-terminal domain for the anti-adenovirus effect. 63b By degrading the virus membrane and recognizing the virus envelop, human GX sPLA 2 is capable of neutralizing HIV-1. 64 Bee and snake venom sPLA 2 s and a peptide derived from bee venom sPLA 2 can block HIV-1 entry into the host cells by steric inhibition of the chemokine receptor on the target cells without requiring enzyme catalytic activity.…”

Section: Secreted Phospholipase A2 (Spla2 Groups I Ii Iii V Ixmentioning

confidence: 99%

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Phospholipase A₂ Enzymes: Physical Structure, Biological Function, Disease Implication, Chemical Inhibition, and Therapeutic Intervention

et al. 2011

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“…Essentially, unlike PLA2G2A, whose tissue expression profiles differ considerably between human and mouse [20], it appears that human and mouse PLA2G3 orthologues (∼82% homology in their core S domain) display a similar, if not entirely identical, tissue distribution pattern. In cell culture systems, forcible expression or exogenous addition of human PLA2G3 facilitates the axonal growth and survival of neuronal cells, proliferation of colorectal cancer cells, maturation of dendritic cells, migration of endothelial cells and inhibition of viral infection, whereas introduction of PLA2G3-directed small interfering RNA partially suppresses some of these events, probably through altering the cellular levels of lysophospholipids or eicosanoids [14,15,37,39,40]. Detection of endogenous PLA2G3 in mouse skin (Figure 3C) raises the intriguing possibility that this unique type of sPLA 2 might function in skin biology.…”

Section: Discussionmentioning

confidence: 99%

Group III secreted phospholipase A2 transgenic mice spontaneously develop inflammation

Sato

Taketomi

Isogai

et al. 2009

Biochemical Journal

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PLA2 (phospholipase A2) group III is an atypical sPLA2 (secretory PLA2) that is homologous with bee venom PLA2 rather than with other mammalian sPLA2s. In the present paper, we show that endogenous group III sPLA2 (PLA2G3) is expressed in mouse skin and that Tg (transgenic) mice overexpressing human PLA2G3 spontaneously develop skin inflammation. Pla2g3-Tg mice over 9 months of age frequently developed dermatitis with hyperkeratosis, acanthosis, parakeratosis, erosion, ulcer and sebaceous gland hyperplasia. The dermatitis was accompanied by infiltration of neutrophils and macrophages and by elevated levels of pro-inflammatory cytokines, chemokines and prostaglandin E2. In addition, Pla2g3-Tg mice had increased lymph aggregates and mucus in the airway, lymphocytic sialadenitis, hepatic extramedullary haemopoiesis, splenomegaly with increased populations of granulocytes and monocytes/macrophages, and increased serum IgG1. Collectively, these observations provide the first demonstration of spontaneous development of inflammation in mice with Tg overexpression of mammalian sPLA2.

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Human group III phospholipase A2 suppresses adenovirus infection into host cells

Cited by 29 publications

References 39 publications

In Vitro Anti-Plasmodium falciparum Properties of the Full Set of Human Secreted Phospholipases A ₂

In Vitro Anti-Plasmodium falciparum Properties of the Full Set of Human Secreted Phospholipases A ₂

Phospholipase A₂ Enzymes: Physical Structure, Biological Function, Disease Implication, Chemical Inhibition, and Therapeutic Intervention

Group III secreted phospholipase A2 transgenic mice spontaneously develop inflammation

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Human group III phospholipase A2 suppresses adenovirus infection into host cells

Cited by 29 publications

References 39 publications

In Vitro Anti-Plasmodium falciparum Properties of the Full Set of Human Secreted Phospholipases A 2

In Vitro Anti-Plasmodium falciparum Properties of the Full Set of Human Secreted Phospholipases A 2

Phospholipase A2 Enzymes: Physical Structure, Biological Function, Disease Implication, Chemical Inhibition, and Therapeutic Intervention

Group III secreted phospholipase A2 transgenic mice spontaneously develop inflammation

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Product

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In Vitro Anti-Plasmodium falciparum Properties of the Full Set of Human Secreted Phospholipases A ₂

In Vitro Anti-Plasmodium falciparum Properties of the Full Set of Human Secreted Phospholipases A ₂

Phospholipase A₂ Enzymes: Physical Structure, Biological Function, Disease Implication, Chemical Inhibition, and Therapeutic Intervention