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

Vaccine Research Center, NIAID, National Institutes of Health, Room 4502, Bldg. 40, MSC-3005, 40 Convent Dr., Bethesda, MD 20892-3005, USA.
Journal of Virology (Impact Factor: 4.44). 03/2007; 81(3):1444-50. DOI: 10.1128/JVI.01790-06
Source: PubMed


Phospholipase A2 (PLA2) proteins affect cellular activation, signal transduction, and possibly innate immunity. A specific secretory PLA2, sPLA2-X, is shown here to neutralize human immunodeficiency virus type 1 (HIV-1) through degradation of the viral membrane. Catalytic
function was required for antiviral activity, and the target cells of infection were unaffected. sPLA2-X potently reduced gene transfer of HIV-1 Env-pseudotyped lentivirus vectors and inhibited the replication of both CCR5-
and CXCR4-tropic HIV-1 in human CD4+ T cells. Virions resistant to damage by antibody and complement were sensitive to lysis by sPLA2-X, suggesting a novel mechanism of antiviral surveillance independent of the acquired immune system.

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Available from: Mark K Louder, Oct 05, 2015
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    • "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. "
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    ABSTRACT: 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. 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. 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.
    AIDS Research and Therapy 11/2009; 6(1):25. DOI:10.1186/1742-6405-6-25 · 1.46 Impact Factor
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    • "Finally, group X sPLA2 (PLA2G10) protein could neutralize several enveloped lentiviruses, including HIV-1, through the phospholipid hydrolysis of the viral membranes [13]. As these in vitro studies suggest, PLA2 enzymes may influence HIV infection. "
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    ABSTRACT: Members of the secreted phospholipase A2 (PLA2) protein family can inhibit HIV-1 virus replication in vitro. To evaluate the impact of PLA2 gene polymorphisms on AIDS disease development, we studied 12 family members using SNPlextrade mark technology that permitted simultaneous typing of 70 tagging Single Nucleotide Polymorphisms (tagSNPs). The study utilized HIV-1 seropositive donors with slow progressor (n=168) or rapid progressor (n=54) status, plus 355 control subjects. All donors were Caucasian (total 577 individuals). Genetic associations yielded mainly 0.01<p<0.05, but lower p-values were obtained for four tagSNPs and seven haplotype alleles. These stronger associations corresponded to both secreted (PLA2G2A, PLA2G2D and PLA2G3) and cytosolic (PLA2G4A and PLA2G6) PLA2 genes, including three (PLA2G2A, PLA2G2D and PLA2G4A) implicated in the pathogenesis of other diseases. Our results suggest that the PLA2 gene family may represent genes of interest for a larger study targeting all the known tagSNPs in the PLA2 genes. The data presented in this study will have to be confirmed in other AIDS cohorts and will also be useful for studies undertaken on the PLA2 gene family in other disease cohorts.
    Biomedecine [?] Pharmacotherapy 01/2008; 62(1):31-40. DOI:10.1016/j.biopha.2007.11.001 · 2.02 Impact Factor
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    ABSTRACT: dsRNA is a by-product of viral replication capable of inducing an inflammatory response when recognized by phagocyte cells. In this study, we identify group IVA cytosolic phospholipase A2 (cPLA2alpha) as an effector of the antiviral response. Treatment of RAW 264.7 murine macrophage-like cells with the dsRNA analog polyinosinic:polycytidylic acid (poly-IC) promotes the release of free arachidonic acid that is subsequently converted into PGE2 by the de novo-synthesized cyclooxygenase-2 (COX-2) enzyme. These processes are blocked by the selective cPLA2alpha inhibitor pyrrophenone, pointing out to cPLA2alpha as the effector involved. In keeping with this observation, the cPLA2alpha phosphorylation state increases after cellular treatment with poly-IC. Inhibition of cPLA2alpha expression and activity by either small interfering RNA (siRNA) or pyrrophenone leads to inhibition of the expression of the inducible NO synthase (iNOS) gene. Moreover, COX-2-derived PGE2 production appears to participate in iNOS expression, because siRNA inhibition of COX-2 also leads to inhibition of iNOS, the latter of which is restored by exogenous addition of PGE2. Finally, cellular depletion of TLR3 by siRNA inhibits COX-2 expression, PGE2 generation, and iNOS induction by poly-IC. Collectively, these findings suggest a model for macrophage activation in response to dsRNA, whereby engagement of TLR3 leads to cPLA2alpha-mediated arachidonic acid mobilization and COX-2-mediated PGE2 production, which cooperate to induce the expression of iNOS.
    The Journal of Immunology 11/2007; 179(7):4821-8. DOI:10.4049/jimmunol.179.7.4821 · 4.92 Impact Factor
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