Corrigendum: Co-stimulation with TLR7 agonist imiquimod and inactivated Influenza virus particles promotes mouse B cell activation, differentiation, and accelerated antigen specific antibody production.

[This corrects the article DOI: 10.3389/fimmu.2018.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection by Intranasal or Intratesticular Route Induces Testicular Damage.

Background: The role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the pathogenesis of testicular damage is uncertain.

Methods: We investigated the virological, pathological, and immunological changes in testes of hamsters challenged by wild-type SARS-CoV-2 and its variants with intranasal or direct testicular inoculation using influenza virus A(H1N1)pdm09 as control.

Results: Besides self-limiting respiratory tract infection, intranasal SARS-CoV-2 challenge caused acute decrease in sperm count, serum testosterone and inhibin B at 4-7 days after infection; and chronic reduction in testicular size and weight, and serum sex hormone at 42-120 days after infection.

Age-associated SARS-CoV-2 breakthrough infection and changes in immune response in a mouse model.

Older individuals are at higher risk of SARS-CoV-2 infection and severe outcomes, but the underlying mechanisms are incompletely understood. In addition, how age modulates SARS-CoV-2 re-infection and vaccine breakthrough infections remain largely unexplored. Here, we investigated age-associated SARS-CoV-2 pathogenesis, immune responses, and the occurrence of re-infection and vaccine breakthrough infection utilizing a wild-type C57BL/6N mouse model.

Low Environmental Temperature Exacerbates Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Golden Syrian Hamsters.

Background: The effect of low environmental temperature on viral shedding and disease severity of Coronavirus Disease 2019 (COVID-19) is uncertain.

Methods: We investigated the virological, clinical, pathological, and immunological changes in hamsters housed at room (21°C), low (12-15°C), and high (30-33°C) temperature after challenge by 105 plaque-forming units of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Results: The nasal turbinate, trachea, and lung viral load and live virus titer were significantly higher (~0.

Cross-linking peptide and repurposed drugs inhibit both entry pathways of SARS-CoV-2.

Up to date, effective antivirals have not been widely available for treating COVID-19. In this study, we identify a dual-functional cross-linking peptide 8P9R which can inhibit the two entry pathways (endocytic pathway and TMPRSS2-mediated surface pathway) of SARS-CoV-2 in cells. The endosomal acidification inhibitors (8P9R and chloroquine) can synergistically enhance the activity of arbidol, a spike-ACE2 fusion inhibitor, against SARS-CoV-2 and SARS-CoV in cells.

H7N9 influenza A virus activation of necroptosis in human monocytes links innate and adaptive immune responses.

We previously demonstrated that avian influenza A H7N9 virus preferentially infected CD14 monocyte in human peripheral blood mononuclear cells (PBMCs), which led to apoptosis. To better understand H7N9 pathogenesis in relation to monocyte cell death, we showed here that extensive phosphorylation of mixed lineage kinase domain-like (MLKL) protein occurred concurrently with the activation of caspases-8, -9 and -3 in H7N9-infected monocytes at 6 h post infection (hpi), indicating that apoptosis and necroptosis pathways were simultaneously activated. The apoptotic morphology was readily observed in H7N9-infected monocytes with transmission electron microscopy (TEM), while the pan-caspase inhibitor, IDN6556 (IDN), accelerated cell death through necroptosis as evidenced by the increased level of pMLKL accompanied with cell swelling and plasma membrane rupture.

Co-stimulation With TLR7 Agonist Imiquimod and Inactivated Influenza Virus Particles Promotes Mouse B Cell Activation, Differentiation, and Accelerated Antigen Specific Antibody Production.

Current influenza vaccines have relatively low effectiveness, especially against antigenically drifted strains, the effectiveness is even lower in the elderly and immunosuppressed individuals. We have previously shown in a randomized clinical trial that the topical application of a toll-like receptor 7 agonist, imiquimod, just before intradermal influenza vaccine could expedite and augment antibody response, including to antigenically-drifted strains. However, the mechanism of this vaccine and imiquimod combination approach is poorly understood.

Prostaglandin E2-Mediated Impairment of Innate Immune Response to A(H1N1)pdm09 Infection in Diet-Induced Obese Mice Could Be Restored by Paracetamol.

Background: Obesity is associated with increased severity of influenza infection. However, the underlying mechanism is largely unknown.

Methods: We employed a mouse model with diet-induced obesity (DIO) to study the innate immune responses induced by influenza virus.

Triple combination of FDA-approved drugs including flufenamic acid, clarithromycin and zanamivir improves survival of severe influenza in mice.

Seasonal influenza virus remains a common cause of mortality despite the use of neuraminidase inhibitors. This study evaluated the efficacy of a triple combination of zanamivir, clarithromycin and flufenamic acid (FFA) in the treatment of influenza virus A(H1N1) infection. An in vitro cell protection assay and a multiple-cycle growth assay showed that the antiviral activity of zanamivir was enhanced when combined with clarithromycin or FFA.

Low population serum microneutralization antibody titer against the predominating influenza A(H3N2) N121K virus during the severe influenza summer peak of Hong Kong in 2017.

The 2017 Hong Kong influenza A(H3N2) summer season was unexpectedly severe. However, antigenic characterization of the 2017 circulating A(H3N2) viruses using ferret antisera did not show significant antigenic drift. We analyzed the hemagglutinin amino acid sequences of A(H3N2) virus circulating in Hong Kong in 2017, and found that viruses with hemagglutinin N121K substitution, which was rare before 2017, emerged rapidly and dominated in 2017 (52.

Avian influenza virus A H7N9 infects multiple mononuclear cell types in peripheral blood and induces dysregulated cytokine responses and apoptosis in infected monocytes.

Most patients with avian influenza A H7N9 virus (H7N9) infection suffer from severe illness, accompanied by dysregulated cytokine/chemokine response, delayed viral clearance and impaired neutralizing antibody response. Here, we evaluated the role of peripheral blood mononuclear cells (PBMCs) in the pathogenesis of H7N9 infection using an ex vivo infection model. H7N9 infected a significantly higher percentage of PBMCs (23.

Suboptimal Humoral Immune Response against Influenza A(H7N9) Virus Is Related to Its Internal Genes.

Influenza A(H7N9) virus pneumonia is associated with a high case fatality rate in humans. Multiple viral factors have been postulated to account for the high virulence of the virus. It has been reported that patients with influenza A(H7N9) virus infection have relatively low titers of neutralizing antibodies compared to those with seasonal influenza virus infections.

Avian influenza A H7N9 virus induces severe pneumonia in mice without prior adaptation and responds to a combination of zanamivir and COX-2 inhibitor.

Background: Human infection caused by the avian influenza A H7N9 virus has a case-fatality rate of over 30%. Systematic study of the pathogenesis of avian H7N9 isolate and effective therapeutic strategies are needed.

Methods: BALB/c mice were inoculated intranasally with an H7N9 virus isolated from a chicken in a wet market epidemiologically linked to a fatal human case, (A/chicken/Zhejiang/DTID-ZJU01/2013 [CK1]), and with an H7N9 virus isolated from a human (A/Anhui/01/2013 [AH1]).

Toll-like receptor 7 agonist imiquimod in combination with influenza vaccine expedites and augments humoral immune responses against influenza A(H1N1)pdm09 virus infection in BALB/c mice.

Toll-like receptors (TLRs) of the innate immune system are known targets for enhancing vaccine efficacy. We investigated whether imiquimod, a synthetic TLR7 agonist, can expedite the immune response against influenza virus infection when combined with influenza vaccine. BALB/c mice were immunized intraperitoneally with monovalent A(H1N1)pdm09 vaccine combined with imiquimod (VCI) prior to intranasal inoculation with a lethal dose of mouse-adapted A(H1N1)pdm09 virus.