Prostaglandin E2 reduces the release and infectivity of new cell-free virions and cell-to-cell HIV-1 transfer
Authors: María Jesús Serramía
Marta Martínez-Bonet
María Ángeles Muñoz-Fernández
María Isabel Clemente
Susana Álvarez
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: HIV-1 infection; prostaglandin E2; signal transduction pathways; antiretrovirals; viral replication
Affiliations: Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain ; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain ; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Zaragoza, Spain.

Abstract:  Background: The course of human immunodeficiency virus type-1 (HIV-1) infection is influenced by a complex interplay between viral and host factors. HIV infection stimulates several proinflammatory genes, such as cyclooxigense-2 (COX-2), which leads to an increase in prostaglandin (PG) levels in the plasma of HIV-1-infected patients. These genes play an indeterminate role in HIV replication and pathogenesis. The effect of prostaglandin E2 (PGE2) on HIV infection is quite controversial and even contradictory, so we sought to determine the role of PGE2 and the signal transduction pathways involved in HIV infection to elucidate possible new targets for antiretrovirals. Results: Our results suggest that PGE2 post-infection treatment acts in the late stages of the viral cycle to reduce HIV replication. Interestingly, viral protein synthesis was not affected, but a loss of progeny virus production was observed. No modulation of CD4 CXCR4 and CCR5 receptor expression, cell proliferation, or activation after PGE2 treatment was detected. Moreover, PGE2 induced an increase in intracellular cAMP (cyclic AMP) levels through the EP2/EP4 receptors. PGE2 effects were mimicked by dbcAMP and by a specific Epac (exchange protein directly activated by cyclic AMP) agonist, 8-Cpt-cAMP. Treatment with PGE2 increased Rap1 activity, decreased RhoA activity and subsequently reduced the polymerization of actin by approximately 30% compared with untreated cells. In connection with this finding, polarized viral assembly platforms enriched in Gag were disrupted, altering HIV cell-to-cell transfer and the infectivity of new virions. Conclusions: Our results demonstrate that PGE2, through Epac and Rap activation, alters the transport of newly synthesized HIV-1 components to the assembly site, reducing the release and infectivity of new cell-free virions and cell-to-cell HIV-1 transfer. 

Retracted: No

PubPeer comments:
 There are two sets of identical actin control blots (please see attached image): first between Figures 2D, 3A, 5B and 7A (red). The second set is between Figures 9A and 9B (blue). The treatments tested are the same, but were all the proteins blotted on the same membrane? Could the authors please comment? ![file] , 
 Not shocking at all for a loading control as it is probably same lysates (as treatment and tissue are the same in both sets). Majority of papers with large western blot figures displays just one loading control band for all protein antibodies assayed (for the same lysates) even if several membranes have been used. Your comment could correspond to almost every papers displaying western blots today. , 
 I disagree with comment #2 by Chrysonephele Palustris. 1. Could the author of the comment provide any data supporting the statement that my initial comment (#1) could correspond to almost every paper displaying western blots? In my experience, most papers employ Western blotting loading controls that - at least judging by the appearance - are derived from the same gel in which the samples of interest had been run. 2. Even if it was a common practice (which, to my knowledge, it is not) to reuse loading controls between gels corresponding to the same experiment, it is definitely not a good practice. For example, please see point 2 in the Cell Press blog post about common mistakes in figure preparation: http: crosstalk.cell.com blog common-pitfalls-in-figure-preparation Below a direct quote from this post:  Therefore, it is rarely appropriate for the same loading control bands to appear in more than one figure panel, and, in an exceptional case, a clear explanation of why it is warranted should be included in the figure legends. ,