Inhibition of Influenza A (H1N1) virus infection by Pt/TiO2-SiO2 Bionanocatalysts

Background: The rapid mutation of the H1N1 strain of the Influenza virus makes it quite difficult to treat once the infection has spread. The development of new treatments based on the destabilization of the genetic material, regardless of the sequence, is necessary. Objective: The study aims to evaluate the antiviral properties of Pt/TiO2-SiO2 bionanocatalysts against Influenza A (H1N1) virus in a post-infection model and to characterize the morphology of the nanoparticles. Methods: The bionanocatalysts were synthesized by the sol-gel method. Electron Microscopy studies were performed to evaluate the grain size and morphology of pure nanoparticles. Madin-Darby Canine Kidney (MDCK) epithelial cells were infected with Influenza A (H1N1) virus. They were treated with 500 μL of three viral suspensions (1:50, 1:100, and 1:1000) and 500 μL of a nanoparticle suspension (2 ng/mL). The presence of the virus was identified by Polymerase Chain Reaction (PCR) endpoint and the antiviral properties of the nanoparticles were identified in terms of infection reduction calculated by real-time PCR using Influenza A and H1N1 subtype primers. The percentage of infection reduction was calculated by comparing control samples and samples treated with the bionanocatalysts. Results: The Pt/TiO2-SiO2 bionanocatalysts showed highly surface-dispersed platinum nanoparticles with an average particle size of 1.23 ± 0.36 nm in the amorphous mixed oxide matrix. The nanoparticles showed antiviral properties with a maximum reduction in viral proliferation of 65.2 ± 3.3%. Conclusion: Pt/TiO2-SiO2 bionanocatalysts were able to reduce Influenza A (H1N1) viral infection 65.2 ± 3.3%; the results suggest the biocompatibility with healthy tissues and in vitro antiviral properties. Further studies should be conducted to identify the concentration required to achieve total virus clearance. However, the outcome of the present work suggests the possibility of implementing bionanocatalysts as treatments for Influenza A (H1N1) virus infection, especially at an advanced stage of infection.

Tetrameric Neuraminidase of Influenza A Virus Is Required to Induce Protective Antibody Responses in Mice

Influenza neuraminidase (NA) is able to induce cross-subtype immunity and is considered as a promising target for the development of universal influenza vaccines. However, commercial influenza vaccines only induced low NA-specific immune responses due to the low amounts and the denatured conformation of NA proteins in current inactivated or split influenza vaccines. Here we investigated the protective efficacy of recombinant tetrameric and monomeric NA proteins to determine whether the conformation contributed to induce protective immunity. We found that H1N1PR8NA tetramer (NAtet) could provide complete homologous protection against A/PR8 (H1N1) virus infection in mice, while the protection of H1N1PR8NA monomer (NAmono) was moderate. Higher levels of NA-reactive binding and inhibition antibodies and less weight loss were observed in the H1N1PR8NAtet-vaccinated group. Similarly, H5N1VNNAtet immunization exhibited a preferable heterologous protection than H5N1VNNAmono, but neither H7N9SHNAtet nor H7N9SHNAmono vaccination showed heterosubtypic protection. We also compared the effect of three adjuvants, aluminum, 3′3′-cGAMP (cGAMP), and Poly(I:C), on the humoral response and protective efficacy induced by H1N1PR8NAtet. H1N1PR8NAtet protein adjuvanted with aluminum was observed to exhibited better capacity in inducing NA-specific humoral immunity and preventing weight loss than with cGAMP or Poly(I:C). In conclusion, our data demonstrate that tetrameric NA with natural conformation is required to induce protective anti-NA immunity. The NA tetramer could provide homologous protection and subtype-specific cross-protection. In addition, the aluminum adjuvant is preferable in recombinant NA protein vaccination.

Hyperacute relapse of Lewis-Sumner syndrome during influenza A (H1N1) virus infection

Background Lewis-Sumner Syndrome (LSS) is considered an asymmetric sensory-motor variant of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), mostly affecting the limbs distally, with electrophysiological evidence of multifocal motor conduction blocks. Cranial nerve involvement is present in a minority. Various well-known infectious agents, directly or via the host’s immune responses, may trigger or exacerbate acute and chronic peripheral neuropathies, which may manifest clinically through a multitude of signs and symptoms. Case presentation We present the case of a 57-year-old male with Lewis-Sumner Syndrome, whose clinical course was quite stable over many years. He developed severe hyperacute relapse of his neuropathic disease in the context of active pneumonia due to influenza A (H1N1) virus infection. During this exacerbation, besides the obvious worsening of the previous asymmetric limb involvement, the patient also manifested left peripheral facial palsy and dysphagia that rapidly evolved over minutes, mimicking a stroke. The patient also showed rapid recovery, with marked improvement of the acute neuropathic dysfunction, immediately after initiation of treatment with oseltamivir. Our hypothesis is that the direct modulation of Na + ion channel activity in the host’s peripheral nerve cell by H1N1 viral proteins could cause acute and potentially reversible dysfunction in the conduction of nerve action potentials. Direct viral neuritis could also have been the cause. Immunomodulatory agents, namely IVIg, were not administered due to the swift clinical improvement noticed in the following days. Conclusions We aim to raise awareness of the possibility of atypical neurological presentations of viral infections, especially relevant in the context of the pandemic the world is now facing.