Effect of Zinc Salts on Respiratory Syncytial Virus Replication

Abstract

Zinc supplementation decreases the morbidity of lower respiratory tract infection in pediatric patients in the developing world. We sought to determine if zinc mediates a specific inhibitory effect against the major cause of pediatric lower respiratory tract disease, respiratory syncytial virus (RSV). We determined the in vitro inhibitory effect of three zinc salts (zinc acetate, lactate, and sulfate) on the replication of RSV at various concentrations of 10 and 1 mM and 100 and 10 M. The degree of inhibition of RSV replication was examined in the presence of zinc during preincubation, adsorption, or penetration and was compared with that caused by salts of other divalent cations. Complete inhibition of RSV plaque formation was observed at 1 and 10 mM, representing reductions that were >10 6 -fold. At the lowest concentration tested, 10 M, we observed >1,000-fold reductions in RSV yield when zinc was present during preincubation, adsorption, penetration, or egress of virus. The therapeutic indices, determined as ratios of 50% toxicity concentration to 50% inhibitory concentration, were 100, 150, and 120 for zinc acetate, zinc lactate, and zinc sulfate, respectively. The inhibitory effect of zinc salts on RSV was concentration dependent and was not observed with other salts containing divalent cations such as calcium, magnesium, and manganese. RSV plaque formation was prevented by pretreatment of HEp-2 cell monolayer cultures with zinc or by addition of zinc to methylcellulose overlay media after infection. The results of this study suggest that zinc mediates antiviral activity on RSV by altering the ability of the cell to support RSV replication.Respiratory syncytial virus (RSV) is the most important viral cause of acute respiratory tract infection (ARI) in infancy and early childhood, with its greatest morbidity in infants (6,8,9). Throughout the world, RSV contributes significantly to annual hospital admissions due to ARI, especially during the epidemic season (18,23,27). In developing countries, malnutrition and deficiencies of micronutrients are associated with increased incidence and severity of ARI (25). Improvement in nutritional status might be a practical strategy for prevention of severe RSV disease in developing countries, if efficacious. At this time, however, we have a poor understanding of the role of micronutrients such as zinc in susceptibility to severe disease caused by RSV infection.Zinc supplementation in children in developing countries was demonstrated to cause a significant reduction in the prevalence of pneumonia (3,20). Zinc has been shown to mediate antiviral effects against certain viruses. Clinical studies showed that zinc significantly shortens the duration of symptoms during rhinovirus infection (17,19,28). Topical application of zinc sulfate also was found in one study to be effective in the treatment of herpes simplex virus (HSV) infection (26). The specific mechanism by which zinc mediated these clinical effects is unknown in most cases. Zinc also enhances the host response to ma...

Interactions between Infections, Nutrients and Xenobiotics

“…Inhibition of DNA replication in S. enteritidis after nitrogen oxide exposure is accompanied by Zn mobilisation, which implies that DNA-binding Zn metalloproteins are critical targets of antimicrobial activity (Schapiro et al, 2003). In accordance with observations in the above studies, electron microscopy studies on HSV have demonstrated massive deposition of Zn onto HSV virions, which interfered with glycoprotein-mediated fusion (Suara and Crowe, 2004).…”

“…Data also show that Ca causes conformation changes in rotaviruses (Pando et al, 2002), Mn causes changes in virulence of HIV (Vartanian et al, 1999), and Cd reactivates latent HSV (Fawl et al, 1996). Moreover, Zn influences gene expression in CMV (Takekoshi et al, 1993) and replication of respiratory syncytical virus (RSV) (Suara and Crowe, 2004). Consequently, in a host of experimental studies several essential (Ca, Cu, Fe, Mn, Se, and Zn) and non-essential (As, Cd, Hg, and Pb) trace elements have been shown to have the capability to influence growth and virulence of various microorganisms (see section "altered virulence of microorganisms caused by nutrients and xenobiotics").…”

Zinc for the treatment of the common cold: a systematic review and meta-analysis of randomized controlled trials

“…Zinc, which can inhibit rhinovirus replication and has activity against other respiratory viruses such as respiratory syncytial virus, 8 is a potential treatment for the common cold. The exact mechanism of zinc's activity on viruses remains uncertain.…”

Pengaruh Suplementasi Seng Terhadap Kejadian Pneumonia pada Penyakit Jantung Bawaan Pirau Kiri ke Kanan

“…30,31 Sama dengan penelitian lain yang menyatakan bahwa pemberian suplementasi seng dapat menghambat kemampuan replikasi dari virus RSV, hasil penelitian secara invitro mendapatkan bahwa seng menghambat replikasi RSV sejak preinkubasi, absorpsi, penetrasi, dan ekskresi. 32 Defisiensi seng dihubungkan dengan atrofi timus, limfopenia, dan penurunan respon imun termediasi sel dan antibodi. Sel epitel timus menghasilkan timulin yang merupakan hormon yang berperan dalam adhesi, migrasi, maturasi, dan peningkatan fungsi sel T. Timulin bergantung pada seng untuk aktivitas biologis yang meliputi induksi perkembangan sel T dan efek anti-inflamasi.…”