Inhibition of rotavirus infection in cultured cells by N-acetyl-cysteine, PPARγ agonists and NSAIDs

Guererero, Carlos A.; Murillo, Andrea; Acosta, Orlando

doi:10.1016/j.antiviral.2012.06.011

Cited by 20 publications

(34 citation statements)

References 84 publications

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“…These molecules are both involved in regulating lipid biosynthesis and metabolism. Rosiglitazone is an FDA-approved diabetes drug that modulates PPAR activity and insulin sensitivity and has been shown to affect RNA virus replication (23–25), virus-induced inflammation (26, 27), and lung inflammation (28–30). Simvastatin is a FDA-approved statin which lowers blood cholesterol by inhibiting 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase.…”

Section: Resultsmentioning

confidence: 99%

Influenza Virus A/Anhui/1/2013 (H7N9) Replicates Efficiently in the Upper and Lower Respiratory Tracts of Cynomolgus Macaques

Wit

Rasmussen

Feldmann

et al. 2014

mBio

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In March 2013, three fatal human cases of infection with influenza A virus (H7N9) were reported in China. Since then, human cases have been accumulating. Given the public health importance of this virus, we performed a pathogenicity study of the H7N9 virus in the cynomolgus macaque model, focusing on clinical aspects of disease, radiographic, histological, and gene expression profile changes in the upper and lower respiratory tracts, and changes in systemic cytokine and chemokine profiles during infection. Cynomolgus macaques developed transient, mild to severe disease with radiographic evidence of pulmonary infiltration. Virus replicated in the upper as well as lower respiratory tract, with sustained replication in the upper respiratory tract until the end of the experiment at 6 days after inoculation. Virus shedding occurred mainly via the throat. Histopathological changes in the lungs were similar to those observed in humans, albeit less severe, with diffuse alveolar damage, infiltration of polymorphonuclear cells, formation of hyaline membranes, pneumocyte hyperplasia, and fibroproliferative changes. Analysis of gene expression profiles in lung lesions identified pathways involved in tissue damage during H7N9 infection as well as leads for development of therapeutics targeting host responses rather than virus replication. Overall, H7N9 infection was not as severe in cynomolgus macaques as in humans, supporting the possible role of underlying medical complications in disease severity as discussed for human H7N9 infection (H. N. Gao et al., N. Engl. J. Med. 368:2277–2285, 2013, doi:10.1056/NEJMoa1305584).

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Section: Resultsmentioning

confidence: 99%

Influenza Virus A/Anhui/1/2013 (H7N9) Replicates Efficiently in the Upper and Lower Respiratory Tracts of Cynomolgus Macaques

Wit

Rasmussen

Feldmann

et al. 2014

mBio

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“…On the other hand, some rotavirus strains have been shown to activate NF-κB (Rollo et al 1999, Halasz et al 2008, Holloway et al 2009, Bagchi et al 2010). Inhibition of rotavirus infectivity in MA104 cells has recently been observed in the presence of NAC (Guerrero et al 2012). Despite these previous findings, further experimental work remains to be done in order to assess the implication of NF-κB activation during rotavirus infection of intestinal villus cells and the NAC contribution in interfering with this particular signal pathway.…”

Section: Discussionmentioning

confidence: 99%

“…ECwt infection of villus cells induced the expression of host-encoded proteins COX-2, ERp57, Hsc70, NF-κB, Hsp70, PDI and PPARγ as detected in cross-sections from intestinal villi. It deserves to be mentioned that Hsc70 and PDI have been identified as rotavirus-interacting proteins during the infection of MA104 cells (Guerrero et al 2002, Calderon et al 2012), whereas COX-2 has been found to be required and induced by rotavirus infection of Caco-2 cells (Rossen et al 2004). On the other hand, the influenza virus-induced ER stress has been associated with increased levels of ER chaperone ERp57 (Roberson et al 2012), whilst recruitment of Hsp70 chaperones has been found to be an important component of viral survival strategies (Mayer 2005).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of rotavirus ECwt infection in ICR suckling mice by N-acetylcysteine, peroxisome proliferator-activated receptor gamma agonists and cyclooxygenase-2 inhibitors

Guerrero

Pardo

Guerrero

2013

Mem. Inst. Oswaldo Cruz

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Live attenuated vaccines have recently been introduced for preventing rotavirus disease in children. However, alternative strategies for prevention and treatment of rotavirus infection are needed mainly in developing countries where low vaccine coverage occurs. In the present work, N-acetylcysteine (NAC), ascorbic acid (AA), some nonsteroidal anti-inflammatory drugs (NSAIDs) and peroxisome proliferator-activated receptor gamma (PPARγ) agonists were tested for their ability to interfere with rotavirus ECwt infectivity as detected by the percentage of viral antigen-positive cells of small intestinal villi isolated from ECwt-infected ICR mice. Administration of 6 mg NAC/kg every 8 h for three days following the first diarrhoeal episode reduced viral infectivity by about 90%. Administration of AA, ibuprofen, diclofenac, pioglitazone or rosiglitazone decreased viral infectivity by about 55%, 90%, 35%, 32% and 25%, respectively. ECwt infection of mice increased expression of cyclooxygenase-2, ERp57, Hsc70, NF-κB, Hsp70, protein disulphide isomerase (PDI) and PPARγ in intestinal villus cells. NAC treatment of ECwt-infected mice reduced Hsc70 and PDI expression to levels similar to those observed in villi from uninfected control mice. The present results suggest that the drugs tested in the present work could be assayed in preventing or treating rotaviral diarrhoea in children and young animals.

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“…To further characterize the etiological agent of acute diarrhea, rotavirus particles were isolated and purified from the patients' stool samples, using a procedure previously reported . The structural proteins associated with the purified virus particles were separated by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS‐PAGE) and then transferred to polyvinylene difluoride membranes before being identified by using antibodies against rotavirus structural proteins …”

Section: Case Reportsmentioning

confidence: 99%

“…Previous research has shown that some cellular proteins such as cyclooxygenase‐2 (COX‐2), nuclear factor κ B (NF‐κB), peroxisome proliferator–activated receptor γ (PPARγ), protein disulfide isomerase (PDI), heat shock protein 90 (Hsp90), heat shock protein 70 (Hsp70), heat shock cognate protein 70 (Hsc70), and heat shock protein 40 (Hsp40) are involved in the rotavirus infection process as studied in cultured cells and mice . We wanted to examine whether the expression level of these cellular proteins was modified by rotavirus infection of villi isolated from stool samples of infected children.…”

Section: Case Reportsmentioning

confidence: 99%

N -Acetylcysteine Treatment of Rotavirus-Associated Diarrhea in Children

et al. 2014

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Rotaviruses are the leading cause of severe, acute, and dehydrating diarrhea affecting children under 5 years of age worldwide. Despite an important reduction in rotavirus-caused deaths as a consequence of the rotavirus vaccine, alternative or complementary strategies for preventing or treating rotavirus-associated diarrhea are needed mainly in the poorest countries. We describe the cases of four rotavirus-unvaccinated 12-13-month-old girls and a 5-year-old boy who developed rotavirus-associated diarrhea confirmed by enzyme-linked immunosorbent assay, Western blotting, and immunochemistry analyses. After the first day of diarrheal episodes, three of the five patients were immediately administered oral N-acetylcysteine (NAC) 60 mg/kg daily, divided into three equal doses every 8 hours. The other two patients did not receive NAC and served as controls. Administration of NAC resulted in a decreased number of diarrheal episodes, excretion of fecal rotavirus antigen, and resolution of symptoms after 2 days of treatment. Our results suggest that NAC treatment after the first diarrheal episode could be an efficient strategy for treating rotavirus-affected children and preventing the associated severe life-threatening accompanying dehydration.

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Inhibition of rotavirus infection in cultured cells by N-acetyl-cysteine, PPARγ agonists and NSAIDs

Cited by 20 publications

References 84 publications

Influenza Virus A/Anhui/1/2013 (H7N9) Replicates Efficiently in the Upper and Lower Respiratory Tracts of Cynomolgus Macaques

Influenza Virus A/Anhui/1/2013 (H7N9) Replicates Efficiently in the Upper and Lower Respiratory Tracts of Cynomolgus Macaques

Inhibition of rotavirus ECwt infection in ICR suckling mice by N-acetylcysteine, peroxisome proliferator-activated receptor gamma agonists and cyclooxygenase-2 inhibitors

N -Acetylcysteine Treatment of Rotavirus-Associated Diarrhea in Children

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