Open Access

Hypothesis of snake and insect venoms against Human Immunodeficiency Virus: a review

  • Ramachandran Meenakshisundaram1,
  • Shah Sweni2, 4, 5Email author and
  • Ponniah Thirumalaikolundusubramanian3
AIDS Research and Therapy20096:25

DOI: 10.1186/1742-6405-6-25

Received: 24 August 2009

Accepted: 19 November 2009

Published: 19 November 2009

Abstract

Background

Snake and insect venoms have been demonstrated to have beneficial effects in the treatment of certain diseases including drug resistant human immunodeficiency virus (HIV) infection. We evaluated and hypothesized the probable mechanisms of venoms against HIV.

Methods

Previous literatures published over a period of 30 years (1979-2009) were searched using the key words snake venom, insect venom, mechanisms and HIV. Mechanisms were identified and discussed.

Results & Conclusion

With reference to mechanisms of action, properties and components of snake venom such as sequence homology and enzymes (protease or L- amino acid oxidase) may have an effect on membrane protein and/or act against HIV at multiple levels or cells carrying HIV virus resulting in enhanced effect of anti-retroviral therapy (ART). This may cause a decrease in viral load and improvement in clinical as well as immunological status. Insect venom and human Phospholipase A2 (PLA2) have potential anti-viral activity through inhibition of virion entry into the cells. However, all these require further evaluation in order to establish its role against HIV as an independent one or as a supplement.

Background

Components of snake venom are used for health and diseases[1], an interesting emerging concept. Some of the snake venom preparations include angiotensin-converting enzyme (ACE) inhibitor, disintegrins (antiplatelet aggregants)[2] and also used, in diagnostic assays of various blood coagulation factors[3]. Alpha neurotoxin, extracted from cobras has been shown to have analgesic effects [4, 5] and crotoxin from Crotalus durissus terrificus has cytotoxic effects[6]. Recently, Alrajhi and Almohaizeie[7] demonstrated the usefulness of snake venom in a patient suffering from a drug resistant human immunodeficiency virus (HIV) infection, who was on anti-retroviral therapy (ART). In HIV patients, the response after administration of snake venom preparation [7, 8] was an increase in CD4 count and decrease in viral load. We have recently shown that the components of snake venom might enhance the activity of ART at different levels[9]. Interestingly, insect venom and human secretions also have anti-HIV activity [1012]. Hence, we evaluated and hypothesized the probable mechanisms of venoms and secretions against HIV infection.

Methods

Previous literatures published over a period of 30 years (1979-2009) were searched using the key words snake venom, insect venom, HIV and mechanisms. Based on the available materials, the probable mechanisms of action of venom and secretions against HIV were identified and discussed.

Results and Discussion

Snake Venom

The pharmacological activities of snake venom are complex in nature with little known about them and it varies amongst the multitude of snake venoms. The mechanisms of action of snake venom against HIV are mediated through various levels [9], such as structural homology, binding interference (receptor/enzyme), catalytic/inhibitory activity through enzymes, and induction/interaction at membrane level.

1) Structure

The HIV virus entry into cells is mediated through the binding of envelope glycoprotein - gp120 [13]. There is a striking homology between the sequence 164-174 of short segment HIV-1 gp120 and the highly conserved 30-40 amino acid residues of snake venom neurotoxins long loop [14, 15]. Thus, both may compete for the same receptor or binding site and act against HIV.

F N I S T S I R G K V - HIV gp 120

C D K F C S I R G P V - alpha - cobratoxin (Naja naja siamensis)

C D A F C S I R G K R - k - bungarotoxin (Bungarus multicintus)

Structure 1: Amino acid sequences of HIV gp120 (164-174) compared to alpha- cobratoxin and k- bungarotoxin (30-40)[15].

2) Binding

  1. a)

    Snake venom contains Phospholipase A2 (PLA2)[11, 16], which protect human primary blood leukocytes from the replication of various macrophage and T cell-tropic human immunodeficiency virus 1 (HIV-1) strains. PLA2 which is found in the venom of many snakes has been shown to block viral entry into cells before virion uncoating through prevention of intracellular release of viral capsid protein [16]. This is mainly due to the specific interaction of PLA2 to host cells and not due to catalytic activity.

     
  2. b)

    Immunokine - an oxidized derivative of alpha - cobra toxin (Naja naja siamensis), has been shown to inhibit the infection of lymphocytes by HIV and Feline immunodeficiency virus (FIV) through chemokine receptors (CCR 5 and CXCR 4) [17].

     

3) Enzymatic activity

  1. a)

    L- amino acid oxidase (LAO), present in the venom of Trimeresurus stejnegeri[18], C. Atrox, P. australis[19]; inhibits infection and replication of HIV virus through P24 antigen in a dose dependant manner[18]. P24 antigen is a core protein of HIV and its level associates with viral load[20]. Besides the binding of protein to cell membrane, hydrogen peroxide (H2O2) produced as a free radical could inhibit the infection/replication of HIV, thereby further enhancing the anti viral activity. In contrast, catalase - a scavenger of H2O2, reduces the anti- viral activity [18].

     
  2. b)

    Protein fragment isolated from Oxyuranus scutellatus snake venom is a potent inhibitor of p24 antigen and blocks viral replication of resistant strains [21].

     
  3. c)

    Snake venom contains metalloprotease inhibitors[16, 22] which could prevent the production of new viruses through inhibition of protease enzymes. HIV infects a CD4 cell of a person's body and then it copies its own genetic code into the cell's DNA. Then, CD4 cell is "programmed" to make new HIV genetic material and proteins. These proteins are degraded by HIV protease enzyme and again these proteins are used to make functional new HIV particles. Protease inhibitors are used to block the protease enzyme and prevent the cell from producing new viruses.

     

4) Effect on membrane protein

P-glycoprotein (P-gp), a membrane protein, is an energy-dependent efflux transporter driven by ATP hydrolysis[23]. P-gp transports a wide range of substances with diverse chemical structures. In general, P-gp substrates appear to be lipophilic and amphiphatic, and are recognized to play an important role in processes of absorption, distribution, metabolism, and excretion of many clinically important drugs in humans [23]. Because of its importance in pharmacokinetics, inhibition or induction of P-gp by various components of snake venom can lead to significant drug-drug interactions, thereby changing the systemic or target tissue exposure of the protease inhibitors. At the same time one has to remember genetic polymorphism of P-gp,[23] which has also been recorded recently, because it may affect drug disposition and produce variable drug effects.

Other Clinical Uses of Snake Venom

Neurotoxins from snake such as cobra venom activates central cholinergic pathways by nicotine and nicotinic agonists, which have been shown to elicit anti-nociceptive effects in a variety of species and produces significant analgesic effect [24, 25]. PLA2 inhibitors (PLI) from snake - Habu snake, Trimeresurus flavoridis have anti-enzymatic, anti-myotoxic, anti-edema inducing, anti-cytotoxic, and anti-bacterial activities - [26], and hence, used in neurodegenerative disorders such as trauma, Alzhiemers disease, Parkinson's and brain tumors - [27]. Fibrolase from A. contorix snake venom degrade α and β chains of fibrin and used as a thrombolytic agent [28]. Snake venom RGD-disintegrins showed direct interaction in several tumor cell lines. It blocks αvβ3 integrin in tumor cells, thus inhibited their adhesion to the extra cellular matrix and thereby prevents metastasis [29]. PLA2 from Bothrops neweidii and Naja Naja venom, was found to be cytotoxic towards B16F10 melanoma and Ehrlich ascitic tumor cells, as an anti-cancer drug [30]. Crotoxin, a pre-synaptic neurotoxin has been tried as an anti-cancer agent in advanced cancer patients [31]. VRCTC-310, a natural product with PLA2 from Crotalus Durissus terrificus and cardiotoxin from Naja Naja atra, have inhibitory effect against human and murine tumor cell lines, and have effective value in the treatment of advanced solid cancers, which were refractory to other therapy [32].

Insect Venom

1. Gene expression

Melittin is a 26 amino acid amphipathic α-helical peptide, a major component of bee venom [33]. The cecropins are a family of antibacterial peptides 35-39 amino acids in length which occur in a number of insect species and in mammals [34]. Like melittin, they consist of two α-helices linked by a flexible segment, and contain amphipathic structures. Melittin and cecropin act against a wide range of infectious agents, including Gram-positive and Gram-negative bacteria [35]. Whereas melittin is lytic for red blood cells at high concentrations, cecropins do not lyse erythrocytes or other eukaryotic cells [35] and appear to be non-toxic for mammalian cells. Melittin has been reported to inhibit replication of murine retroviruses, tobacco mosaic virus [36] and herpes simplex virus [37] suggesting that melittin also displays antiviral activity. Analogous to antibacterial activity, the antiviral activity of melittin has been attributed to direct lysis of viral membranes, as demonstrated for murine retroviruses [38]. However, melittin also displays antiviral activity at much lower, non-virolytic concentrations, as shown for T cells chronically infected with HIV-1 [39]. Wachinger [10] et al., reported that melittin and cecropin A are shown to suppress production of HIV-1 by acutely infected cells and also, suppresses the HIV-1 replication by interfering with host cell-directed viral gene expression [10]. Melittin treatment of T cells reduces levels of intracellular Gag and viral mRNAs, and decreases HIV long terminal repeat (LTR) activity. Besides, HIV LTR activity is also reduced in human cells stably transfected with melittin and cecropin genes.

2. Binding

  1. i.

    Mammalian venom secreted PLA2 have been associated with a variety of biological effects. Fernard et al [11] suggested that PLA2 protect human blood leukocytes from the replication of various macrophage and T cell-tropic HIV-1 strains. This is neither due to virucidal nor cytotoxic effect on host cells; however PLA2 blocks viral entry into cells before virion uncoating, independent of the receptor. Inhibitors and catalytic products of PLA2 have no effect on HIV-1 infection suggesting that PLA2 catalytic activity is not involved in antiviral effect.

     
  2. ii.

    Peptide p3bv, is a 21-25 aminoacids component from secreted phospholipases of bee venom (bvPLA2) [40]. The p3bv peptide inhibits the replication of HIV-1 through prevention of the cell fusion process mediated by T-lymphotropic HIV-1 envelope without the effect of monocytotropic HIV-1. Then, p3bv inhibits the binding of stromal cell factor-1 α (natural ligand of CXCR4) and 12G5 (anti-CXCR4 monoclonal antibody). Overall, p3bv blocks the replication of T-lymphotropic HIV-1 strains by interacting with CXCR4, thereby blocking viral entry into cells.

     
  3. iii.

    PLA2-I A from bee, and serpent venom showed in vitro anti-HIV activity, which was due to the ability of secretions to destabilize anchorage (heparans) and fusion (cholesterol) receptors on HIV target cells [41].

     

Human PLA2

Interestingly, human PLA2 (group III PLA2) has significant homology with bee venom PLA2 [42]. Several murine and human group phospholipases such as II A, X, V, XII, II E, I B, and II F have potential antibacterial effects against gram positive and negative bacteria [43]. In individuals repeatedly exposed to HIV but who remain uninfected, several possible reasons for protection have been proposed but not clearly elucidated [44].

1. Membrane

Kim et al., [12] suggested that human PLA2 and human group X PLA2 (PLA2-X) have potential antiviral activity against diverse lentiviruses by the degradation of viral membrane. PLA2-X has high affinity for phosphatidylcholine, a phospholipid in outer plasma membrane and hydrolyzes it. Viral membrane of HIV- 1 is rich in phosphatidylcholine and sphingomyelin and may be more susceptible to PLA2-X.

2. Binding

PLA2-X inhibits replication of both CXCR4 and CCR5 HIV-1 in human CD4 cells. This effect was observed despite the resistance of viral preparations to lysis by antibody-mediated complement activation, suggesting that this action occur in cases even where the acquired immunity is ineffective[12]. In view of the above, anitiviral activity of human PLA2 expressed in immune tissues and cells will be particularly interesting to analyze in future [44].

Debate in PLA2 action

Kim et al., [12] concluded that enzymatic activity of PLA2-X is necessary for antiviral effect, which contradict the findings of Fernard et al., [11] where catalytic activity was not required. Hence, further studies are needed to ascertain its exact mechanism.

Conclusion

In view of the above mechanisms, snake venom might reduce HIV load, thereby decreasing its effect and enhances CD4 count. Insect venom and human PLA2 act through PLA2 mediated inhibition of virion entry into host cells. Hopefully, the use of venom preparation or a synthetic molecule similar to snake/insect venom/human secretions without adverse effects may open a new era of anti-retroviral therapy against HIV or act as an adjuvant not only for HIV but also to other viral infections. However, further research is required to ascertain the exact mechanism of antiviral activity of snake and insect venoms.

Financial disclosure

Nil

List of abbreviations

HIV: 

human immunodeficiency virus

ART: 

anti-retroviral therapy

PLA2

Phospholipase A2

HIV-1: 

human immunodeficiency virus 1

ACE: 

angiotensin-converting enzyme

FIV: 

Feline immunodeficiency virus

LAO: 

L- amino acid oxidase

H2O2: 

hydrogen peroxide

P-gp: 

P-glycoprotein

PLI: 

PLA2 inhibitors

LTR: 

long terminal repeat

bvPLA2

phospholipases of bee venom

PLA2-X: 

human group X PLA2.

Declarations

Authors’ Affiliations

(1)
Madras Medical College
(2)
University of Debrecen, Medical & Health Science Center
(3)
Chennai Medical College Hospital & Research Center
(4)
(5)
Simonyi utca

References

  1. Koh D, Armugam A, Jeyaseelan K: Snake venom components and their applications in biomedicine. Cell Mol Life Sci. 2006, 63 (24): 3030-3041. 10.1007/s00018-006-6315-0View ArticlePubMedGoogle Scholar
  2. Patlak M: From viper's venom to drug design: treating hypertension. FASEB J. 2004, 18 (3): 421- 10.1096/fj.03-1398bktView ArticlePubMedGoogle Scholar
  3. Marsh NA: Diagnostic uses of snake venom. Haemostasis. 2001, 31 (3-6): 211-217.PubMedGoogle Scholar
  4. Chen ZX, Zhang HL, Gu ZL, Chen BW, Han R, Reid PF, Raymond LN, Qin ZH: A long-form alpha-neurotoxin from cobra venom produces potent opioid-independent analgesia. Acta Pharmacol Sin. 2006, 27 (4): 402-408. 10.1111/j.1745-7254.2006.00293.xView ArticlePubMedGoogle Scholar
  5. Pu XC, Wong PT, Gopalakrishnakone P: A novel analgesic toxin (hannalgesin) from the venom of king cobra (Ophiophagus hannah). Toxicon. 1995, 33 (11): 1425-1431. 10.1016/0041-0101(95)00096-5View ArticlePubMedGoogle Scholar
  6. Faure G, Harvey AL, Thomson E, Saliou B, Radvyani F, Bon C: Comparison of crotoxin isoforms reveals that stability of the complex plays a major role in its pharmacological action. Eur J Biochem. 1993, 214 (2): 491-496. 10.1111/j.1432-1033.1993.tb17946.xView ArticlePubMedGoogle Scholar
  7. Alrajhi AA, Almohaizeie A: Snake venom preparation for drug-resistant human immunodeficiency virus. Ann Saudi Med. 2008, 28 (4): 292-293. 10.4103/0256-4947.51714View ArticlePubMedGoogle Scholar
  8. Samayz.http://www.samayz-ksa.com/index.html
  9. Meenakshisundaram R, Uma A, Thirumalaikolundusubramanian P: RE: Snake venom preparation for drug-resistant human immunodeficiency virus. Ann Saudi Med. 2009, 29 (2): 159- 10.4103/0256-4947.51791PubMed CentralView ArticlePubMedGoogle Scholar
  10. Wachinger M, Kleinschmidt A, Winder D, von Pechmann N, Ludvigsen A, Neumann M, Holle R, Salmons B, Erfle V, Brack-Werner R: Antimicrobial peptides melittin and cecropin inhibit replication of human immunodeficiency virus 1 by suppressing viral gene expression. J Gen Virol. 1998, 79 (Pt 4): 731-740.View ArticlePubMedGoogle Scholar
  11. Fenard D, Lambeau G, Valentin E, Lefebvre JC, Lazdunski M, Doglio A: Secreted phospholipases A(2), a new class of HIV inhibitors that block virus entry into host cells. J Clin Invest. 1999, 104 (5): 611-618. 10.1172/JCI6915PubMed CentralView ArticlePubMedGoogle Scholar
  12. Kim JO, Chakrabarti BK, Guha-Niyogi A, Louder MK, Mascola JR, Ganesh L, Nabel GJ: Lysis of human immunodeficiency virus type 1 by a specific secreted human phospholipase A2. J Virol. 2007, 81 (3): 1444-1450. 10.1128/JVI.01790-06PubMed CentralView ArticlePubMedGoogle Scholar
  13. Kwong PD, Wyatt R, Robinson J, Sweet RW, Sodroski J, Hendrickson WA: Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature. 1998, 393 (6686): 648-659. 10.1038/31405View ArticlePubMedGoogle Scholar
  14. Sönnerborg A, Johansson B: The neurotoxin-like sequence of human immunodeficiency virus GP120: A comparison of sequence data from patients with and without neurological symptoms. Virus Genes. 1993, 7 (1): 23-31. 10.1007/BF01702346View ArticlePubMedGoogle Scholar
  15. Neri P, Bracci L, Rustici M, Santucci A: Sequence homology between HIV gp120, rabies virus glycoprotein, and snake venom neurotoxins. Archives of Virology. 1990, 114 (3): 265-269. 10.1007/BF01310756View ArticlePubMedGoogle Scholar
  16. da Silva JO, Fernandes RS, Ticli FK, Oliveira CZ, Mazzi MV, Franco JJ, Giuliatti S, Pereira PS, Soares AM, Sampaio SV: Triterpenoid saponins, new metalloprotease snake venom inhibitors isolated from Pentaclethra macroloba. Toxicon. 2007, 50 (2): 283-291. 10.1016/j.toxicon.2007.03.024View ArticlePubMedGoogle Scholar
  17. Esperanza NeuroPeptides.http://www.esperanzapeptide.net/news.php
  18. Zhang YJ, Wang JH, Lee WH, Wang Q, Liu H, Zheng YT, Zhang Y: Molecular characterization of Trimeresurus stejnegeri venom L-amino acid oxidase with potential anti-HIV activity. Biochem Biophys Res Commun. 2003, 309 (3): 598-604. 10.1016/j.bbrc.2003.08.044View ArticlePubMedGoogle Scholar
  19. Du XY, Clemetson KJ: Snake venom L-amino acid oxidases. Toxicon. 2002, 40 (6): 659-665. 10.1016/S0041-0101(02)00102-2View ArticlePubMedGoogle Scholar
  20. Brown AE, Vahey MT, Zhou SY, Chung RC, Ruiz NM, Hofheinz D, Lane JR, Mayers DL: Quantitative relationship of circulating p24 antigen with human immunodeficiency virus (HIV) RNA and specific antibody in HIV-infected subjects receiving antiretroviral therapy. The RV43 Study Group. J Infect Dis. 1995, 172 (4): 1091-1095.View ArticlePubMedGoogle Scholar
  21. Ophidia products Inc.http://ophidia.com/novel_synth.html
  22. Fenard DL, Valentin E, Lefebvre JC, Lazdunski M, Doglio A: Secreted phospholipases A(2), a new class of HIV inhibitors that block virus entry into host cells. J Clin Invest. 1999, 104: 611-618. 10.1172/JCI6915PubMed CentralView ArticlePubMedGoogle Scholar
  23. Tandon V, Kapoor B, Bano G, Gupta S, Gillani Z, Kour D: P-glycoprotein: Pharmacological relevance. Indian Journal of Pharmacology. 2006, 38 (1): 13-24. 10.4103/0253-7613.19847.View ArticleGoogle Scholar
  24. Damaj MI, Meyer EM, Martin BR: The antinociceptive effects of alpha7 nicotinic agonists in an acute pain model. Neuropharmacology. 2000, 39 (13): 2785-2791. 10.1016/S0028-3908(00)00139-8View ArticlePubMedGoogle Scholar
  25. Decker MW, Meyer MD, Sullivan JP: The therapeutic potential of nicotinic acetylcholine receptor agonists for pain control. Expert Opin Investig Drugs. 2001, 10 (10): 1819-1830. 10.1517/13543784.10.10.1819View ArticlePubMedGoogle Scholar
  26. Soares AM, Marcussi S, Stabeli RG, Franca SC, Giglio JR, Ward RJ, Arantes EC: Structural and functional analysis of BmjMIP, a phospholipase A2 myotoxin inhibitor protein from Bothrops moojeni snake plasma. Biochem Biophys Res Commun. 2003, 302 (2): 193-200. 10.1016/S0006-291X(03)00155-4View ArticlePubMedGoogle Scholar
  27. Farooqui AA, Litsky ML, Farooqui T, Horrocks LA: Inhibitors of intracellular phospholipase A2 activity: their neurochemical effects and therapeutical importance for neurological disorders. Brain Res Bull. 1999, 49 (3): 139-153. 10.1016/S0361-9230(99)00027-1View ArticlePubMedGoogle Scholar
  28. Samsa GP, Matchar DB, Williams GR, Levy DE: Cost-effectiveness of ancrod treatment of acute ischaemic stroke: results from the Stroke Treatment with Ancrod Trial (STAT). J Eval Clin Pract. 2002, 8 (1): 61-70. 10.1046/j.1365-2753.2002.00315.xView ArticlePubMedGoogle Scholar
  29. Yeh CH, Peng HC, Yang RS, Huang TF: Rhodostomin, a snake venom disintegrin, inhibits angiogenesis elicited by basic fibroblast growth factor and suppresses tumor growth by a selective alpha(v)beta(3) blockade of endothelial cells. Molecular pharmacology. 2001, 59 (5): 1333-1342.PubMedGoogle Scholar
  30. Basavarajappa BS, Gowda TV: Comparative characterization of two toxic phospholipases A2 from Indian cobra (Naja naja naja) venom. Toxicon. 1992, 30 (10): 1227-1238. 10.1016/0041-0101(92)90439-CView ArticlePubMedGoogle Scholar
  31. Cura JE, Blanzaco DP, Brisson C, Cura MA, Cabrol R, Larrateguy L, Mendez C, Sechi JC, Silveira JS, Theiller E: Phase I and pharmacokinetics study of crotoxin (cytotoxic PLA(2), NSC-624244) in patients with advanced cancer. Clin Cancer Res. 2002, 8 (4): 1033-1041.PubMedGoogle Scholar
  32. Costa LA, Miles HA, Diez RA, Araujo CE, Coni Molina CM, Cervellino JC: Phase I study of VRCTC-310, a purified phospholipase A2 purified from snake venom, in patients with refractory cancer: safety and pharmacokinetic data. Anti-cancer drugs. 1997, 8 (9): 829-834. 10.1097/00001813-199710000-00003View ArticlePubMedGoogle Scholar
  33. Bazzo R, Tappin MJ, Pastore A, Harvey TS, Carver JA, Campbell ID: The structure of melittin. A 1H-NMR study in methanol. Eur J Biochem. 1988, 173 (1): 139-146. 10.1111/j.1432-1033.1988.tb13977.xView ArticlePubMedGoogle Scholar
  34. Boman HG: Peptide antibiotics and their role in innate immunity. Annu Rev Immunol. 1995, 13: 61-92. 10.1146/annurev.iy.13.040195.000425View ArticlePubMedGoogle Scholar
  35. Wade D, Andreu D, Mitchell SA, Silveira AM, Boman A, Boman HG, Merrifield RB: Antibacterial peptides designed as analogs or hybrids of cecropins and melittin. Int J Pept Protein Res. 1992, 40 (5): 429-436.View ArticlePubMedGoogle Scholar
  36. Marcos JF, Beachy RN, Houghten RA, Blondelle SE, Perez-Paya E: Inhibition of a plant virus infection by analogs of melittin. Proc Natl Acad Sci USA. 1995, 92 (26): 12466-12469. 10.1073/pnas.92.26.12466PubMed CentralView ArticlePubMedGoogle Scholar
  37. Baghian A, Jaynes J, Enright F, Kousoulas KG: An amphipathic alpha-helical synthetic peptide analogue of melittin inhibits herpes simplex virus-1 (HSV-1)-induced cell fusion and virus spread. Peptides. 1997, 18 (2): 177-183. 10.1016/S0196-9781(96)00290-2View ArticlePubMedGoogle Scholar
  38. Esser AF, Bartholomew RM, Jensen FC, Muller-Eberhard HJ: Disassembly of viral membranes by complement independent of channel formation. Proc Natl Acad Sci USA. 1979, 76 (11): 5843-5847. 10.1073/pnas.76.11.5843PubMed CentralView ArticlePubMedGoogle Scholar
  39. Wachinger M, Saermark T, Erfle V: Influence of amphipathic peptides on the HIV-1 production in persistently infected T lymphoma cells. FEBS letters. 1992, 309 (3): 235-241. 10.1016/0014-5793(92)80780-KView ArticlePubMedGoogle Scholar
  40. Fenard D, Lambeau G, Maurin T, Lefebvre JC, Doglio A: A peptide derived from bee venom-secreted phospholipase A2 inhibits replication of T-cell tropic HIV-1 strains via interaction with the CXCR4 chemokine receptor. Mol Pharmacol. 2001, 60 (2): 341-347.PubMedGoogle Scholar
  41. Villarubia VGCL, Diez RA: Secreted phospholipases A2 (sPLA2): friends or foes? Are they actors in antibacterial and anti-HIV resistance?. Med Clin (Barc). 2004, 123 (19): 749-757. 10.1157/13069312Google Scholar
  42. Valentin E, Ghomashchi F, Gelb MH, Lazdunski M, Lambeau G: Novel human secreted phospholipase A(2) with homology to the group III bee venom enzyme. J Biol Chem. 2000, 275 (11): 7492-7496. 10.1074/jbc.275.11.7492View ArticlePubMedGoogle Scholar
  43. Koduri RS, Gronroos JO, Laine VJ, Le Calvez C, Lambeau G, Nevalainen TJ, Gelb MH: Bactericidal properties of human and murine groups I, II, V, X, and XII secreted phospholipases A(2). J Biol Chem. 2002, 277 (8): 5849-5857. 10.1074/jbc.M109699200View ArticlePubMedGoogle Scholar
  44. Stranford SA, Skurnick J, Louria D, Osmond D, Chang SY, Sninsky J, Ferrari G, Weinhold K, Lindquist C, Levy JA: Lack of infection in HIV-exposed individuals is associated with a strong CD8(+) cell noncytotoxic anti-HIV response. Proc Natl Acad Sci USA. 1999, 96 (3): 1030-1035. 10.1073/pnas.96.3.1030PubMed CentralView ArticlePubMedGoogle Scholar

Copyright

© Meenakshisundaram et al; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.