The contribution of peroxynitrite generation in HIV replication in human primary macrophages

Stefano Aquaro, Carolina Muscoli, Alessandro Ranazzi, Michela Pollicita, Teresa Granato, Laura Masuelli, Andrea Modesti, Carlo Federico Perno, Vincenzo Mollace

Research output: Contribution to journalArticle

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Abstract

Background: Monocytes/Macrophages (M/M) play a pivotal role as a source of virus during the whole course of HIV-1 infection. Enhanced oxidative stress is involved in the pathogenesis of HIV-1 infection. HIV-1 regulatory proteins induce a reduction of the expression and the activity of MnSOD, the mitochondrial isoform leading to a sustained generation of superoxide anions and peroxynitrite that represent important mediators of HIV-1 replication in M/M. MnTBAP (Mn(III)tetrakis(4-benzoic acid)porphrin chloride), a synthetic peroxynitrite decomposition catalyst, reduced oxidative stress subsequent to peroxynitrite generation. Results: Virus production was assessed by p24 ELISA, western blot, and electron microscopy during treatment with MnTBAP. MnTBAP treatment showed a reduction of HIV-1 replication in both acutely and chronically infected M/M: 99% and 90% inhibition of p24 released in supernatants compared to controls, respectively. Maturation of p55 and p24 was strongly inhibited by MnTBAP in both acutely and chronically infected M/ M. EC50 and EC90 are 3.7 (± 0.05) μM and 19.5 (± 0.5) μM, in acutely infected M/M; 6.3 (± 0.003) μM and 30 (± 0.6) μM, in chronically infected M/M. In acutely infected peripheral blood limphocytes (PBL), EC50 and EC90 are 7.4 (± 0.06) μM and of 21.3 (± 0.6) μM, respectively. Treatment of acutely-infected M/M with MnTBAP inhibited the elevated levels of malonildialdehyde (MDA) together with the nitrotyrosine staining observed during HIV-1 replication. MnTBAP strongly reduced HIV-1 particles in infected M/M, as shown by electron microscopy. Moreover, in presence of MnTBAP, HIV-1 infectivity was reduced of about 1 log compared to control. Conclusion: Results supportthe role of superoxide anions in HIV-1 replication in M/M and suggest that MnTBAP may counteract HIV-1 replication in combination with other antiretroviral treatments.

Original languageEnglish
Article number76
JournalRetrovirology
Volume4
DOIs
Publication statusPublished - Oct 21 2007

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Peroxynitrous Acid
HIV-1
Macrophages
HIV
Monocytes
Superoxides
HIV Infections
Electron Microscopy
Oxidative Stress
Viruses
Benzoic Acid
manganese(III)-tetrakis(4-benzoic acid)porphyrin
Therapeutics
Chlorides
Protein Isoforms
Western Blotting
Enzyme-Linked Immunosorbent Assay
Staining and Labeling

ASJC Scopus subject areas

  • Virology

Cite this

Aquaro, S., Muscoli, C., Ranazzi, A., Pollicita, M., Granato, T., Masuelli, L., ... Mollace, V. (2007). The contribution of peroxynitrite generation in HIV replication in human primary macrophages. Retrovirology, 4, [76]. https://doi.org/10.1186/1742-4690-4-76

The contribution of peroxynitrite generation in HIV replication in human primary macrophages. / Aquaro, Stefano; Muscoli, Carolina; Ranazzi, Alessandro; Pollicita, Michela; Granato, Teresa; Masuelli, Laura; Modesti, Andrea; Perno, Carlo Federico; Mollace, Vincenzo.

In: Retrovirology, Vol. 4, 76, 21.10.2007.

Research output: Contribution to journalArticle

Aquaro, S, Muscoli, C, Ranazzi, A, Pollicita, M, Granato, T, Masuelli, L, Modesti, A, Perno, CF & Mollace, V 2007, 'The contribution of peroxynitrite generation in HIV replication in human primary macrophages', Retrovirology, vol. 4, 76. https://doi.org/10.1186/1742-4690-4-76
Aquaro S, Muscoli C, Ranazzi A, Pollicita M, Granato T, Masuelli L et al. The contribution of peroxynitrite generation in HIV replication in human primary macrophages. Retrovirology. 2007 Oct 21;4. 76. https://doi.org/10.1186/1742-4690-4-76
Aquaro, Stefano ; Muscoli, Carolina ; Ranazzi, Alessandro ; Pollicita, Michela ; Granato, Teresa ; Masuelli, Laura ; Modesti, Andrea ; Perno, Carlo Federico ; Mollace, Vincenzo. / The contribution of peroxynitrite generation in HIV replication in human primary macrophages. In: Retrovirology. 2007 ; Vol. 4.
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AU - Masuelli, Laura

AU - Modesti, Andrea

AU - Perno, Carlo Federico

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