Zinc Potentiates the Antiviral Action of Human IFN-<i>α</i>Tenfold

Berg, Kurt; Bolt, Gert; Andersen, Henning; Owen, Terence C.

doi:10.1089/10799900152434330

Cited by 69 publications

(56 citation statements)

References 14 publications

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“…Zinc deficiency affects both innate and adaptive immune systems and induces oxidative stress in humans and animals, which can be corrected by zinc supplementation (15,27,28). Zinc has been reported to potentiate the antiviral action of human alpha interferon (IFN-␣), alleviate the symptoms of rhinovirus-induced colds, and increase the response rate of IFN-␣ therapy in chronic hepatitis C cases, and topical zinc treatment has been used to control HSV infection (18,(29)(30)(31). Although several reports have demonstrated the inhibitory effect of zinc salts on viral replication, very few studies have identified the underlying mechanism.…”

Section: Discussionmentioning

confidence: 99%

Zinc Salts Block Hepatitis E Virus Replication by Inhibiting the Activity of Viral RNA-Dependent RNA Polymerase

Kaushik

Subramani

Anang

et al. 2017

J Virol

125

117

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Hepatitis E virus (HEV) causes an acute, self-limiting hepatitis in healthy individuals and leads to chronic disease in immunocompromised individuals. HEV infection in pregnant women results in a more severe outcome, with the mortality rate going up to 30%. Though the virus usually causes sporadic infection, epidemics have been reported in developing and resource-starved countries. No specific antiviral exists against HEV. A combination of interferon and ribavirin therapy has been used to control the disease with some success. Zinc is an essential micronutrient that plays crucial roles in multiple cellular processes. Zinc salts are known to be effective in reducing infections caused by few viruses. Here, we investigated the effect of zinc salts on HEV replication. In a human hepatoma cell (Huh7) culture model, zinc salts inhibited the replication of genotype 1 (g-1) and g-3 HEV replicons and g-1 HEV infectious genomic RNA in a dose-dependent manner. Analysis of a replication-defective mutant of g-1 HEV genomic RNA under similar conditions ruled out the possibility of zinc salts acting on replication-independent processes. An ORF4-Huh7 cell line-based infection model of g-1 HEV further confirmed the above observations. Zinc salts did not show any effect on the entry of g-1 HEV into the host cell. Furthermore, our data reveal that zinc salts directly inhibit the activity of viral RNA-dependent RNA polymerase (RdRp), leading to inhibition of viral replication. Taken together, these studies unravel the ability of zinc salts in inhibiting HEV replication, suggesting their possible therapeutic value in controlling HEV infection. Hepatitis E virus (HEV) is a public health concern in resource-starved countries due to frequent outbreaks. It is also emerging as a health concern in developed countries owing to its ability to cause acute and chronic infection in organ transplant and immunocompromised individuals. Although antivirals such as ribavirin have been used to treat HEV cases, there are known side effects and limitations of such therapy. Our discovery of the ability of zinc salts to block HEV replication by virtue of their ability to inhibit the activity of viral RdRp is important because these findings pave the way to test the efficacy of zinc supplementation therapy in HEV-infected patients. Since zinc supplementation therapy is known to be safe in healthy individuals and since high-dose zinc is used in the treatment of Wilson's disease, it may be possible to control HEV-associated health problems following a similar treatment regimen.

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Section: Discussionmentioning

confidence: 99%

Zinc Salts Block Hepatitis E Virus Replication by Inhibiting the Activity of Viral RNA-Dependent RNA Polymerase

Kaushik

Subramani

Anang

et al. 2017

J Virol

125

117

View full text Add to dashboard Cite

show abstract

“…Zinc has immunomodulatory effects that could counteract viral infections by having an effect on the synthesis of cytokines. In vitro , zinc induces the production of antiviral interferon (IFN)‐α as well as IFN‐γ and it can potentiate the antiviral action of IFN‐α 24–26 . In addition, clearance of viral infections requires cytotoxic T lymphocytes, which are highly dependent on zinc 26 .…”

Section: Discussionmentioning

confidence: 99%

Oral zinc sulfate treatment for viral warts: An open-label study

Mun

Kim

Jung

et al. 2010

The Journal of Dermatology

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Viral warts, which are caused by the human papilloma virus, are a common problem in dermatology. Various modalities have been used to treat warts, but none are uniformly effective or directly antiviral. Recent studies show that oral zinc sulfate could be effective in the treatment of viral warts. Thirty-one patients with multiple, non-genital viral warts were recruited in this open-label clinical study. The patients were treated with oral zinc sulfate (10 mg/kg to a maximum dose of 600 mg/day) for 2 months and followed up with assessments for the resolution of their warts and for any evidence of recurrence after treatment. Among the 31 patients, 18 patients showed low serum zinc levels (58%). Of 26 patients who completed the study (84%), 13 (50%) showed complete resolution of their warts after 2 months of treatment. Complete responders remained free of lesions at 6-month follow-up. No serious side-effects were reported apart from nausea (16%), mild gastric pain (3%) and itching sensation (3%). Oral zinc sulfate was found to be a good option in the treatment of viral warts, as it was safe and effective without important side-effects.

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“…In vitro, zinc induces the production of antiviral interferon (IFN)-α as well as IFN-γ [19,136] and it can potentiate the antiviral action of IFN-α, but not of IFN-γ [11]. Besides this, clearance of viral infections requires cytotoxic T lymphocytes, which are highly dependent on zinc, as discussed above.…”

Section: Viral Infectionsmentioning

confidence: 99%

Modulating the immune response by oral zinc supplementation: a single approach for multiple diseases

Overbeck

Rink

Haase

2008

Arch. Immunol. Ther. Exp.

182

124

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Zinc is required for multiple cellular tasks, and especially the immune system depends on a sufficient availability of this essential trace element. During the last decades, many studies attempted to affect the outcome of various diseases by zinc supplementation. These efforts either aimed at supporting immunity by zinc administration or at correcting a loss of zinc secondary to the disease to restore the zinc-dependent functions of the immune system. This review aims to summarize the respective findings and to discuss possible molecular mechanisms by which zinc could influence viral, bacterial, and parasitic infections, autoimmune diseases, and the response to vaccination. Zinc supplementation in diseases such as diarrhea, chronic hepatitis C, shigellosis, leprosy, tuberculosis, pneumonia, acute lower respiratory infection, and leishmaniasis seems beneficial. In contrast, the results for the common cold and malaria are still not conclusive, and zinc was ineffective in most vaccination and rheumatoid arthritis studies. For AIDS and type 1 diabetes, zinc supplementation may even be a risk factor for increased mortality or deterioration of the glucose metabolism, respectively. In these cases, zinc supplementation should be used with care and limited to clearly zinc-deficient individuals.

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Zinc Potentiates the Antiviral Action of Human IFN-αTenfold

Cited by 69 publications

References 14 publications

Zinc Salts Block Hepatitis E Virus Replication by Inhibiting the Activity of Viral RNA-Dependent RNA Polymerase

Zinc Salts Block Hepatitis E Virus Replication by Inhibiting the Activity of Viral RNA-Dependent RNA Polymerase

Oral zinc sulfate treatment for viral warts: An open-label study

Modulating the immune response by oral zinc supplementation: a single approach for multiple diseases

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