Influenza–Host Interplay and Strategies for Universal Vaccine Development

Abstract

Influenza is an annual epidemic and an occasional pandemic caused by pathogens that are responsible for infectious respiratory disease. Humans are highly susceptible to the infection mediated by influenza A viruses (IAV). The entry of the virus is mediated by the influenza virus hemagglutinin (HA) glycoprotein that binds to the cellular sialic acid receptors and facilitates the fusion of the viral membrane with the endosomal membrane. During IAV infection, virus-derived pathogen-associated molecular patterns (PAMPs) are recognized by host intracellular specific sensors including toll-like receptors (TLRs), C-type lectin receptors, retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) either on the cell surface or intracellularly in endosomes. Herein, we comprehensively review the current knowledge available on the entry of the influenza virus into host cells and the molecular details of the influenza virus–host interface. We also highlight certain strategies for the development of universal influenza vaccines.

Endocytosis of abiotic nanomaterials and nanobiovectors: Inhibition of membrane trafficking

“… Virus Family Receptor Mechanism Ref. Vesicular stomatitis virus Rhabdoviridae Low-density lipoprotein receptors (LDL-R) Clathrin-mediated [189] Dengue Virus Flaviviridae GAG, DC-SIGN and other C-Type lectin receptors Clathrin-mediated [190] , [191] Influenza A virus Myxoviridae Sialic acid containing receptors Clathrin-mediated, Macropinocytosis [192] Simian Virus 40 Poliomaviridae GM1 ganglioside Caveolae-mediated [193] , [194] ZIKA virus Flaviviridae DC-SIGN and other C-type lectin receptors, TIM and TAM receptors Clathrin-mediated, Caveolae-mediated [195] , [196] Mayaro virus Alphaviridae Matrix Remodeling Associated 8 (MXRA8) Clathrin-mediated, Caveolae-mediated [197] HCoV-OC43 Betacoronaviridae Sialoglycan-based receptors Caveolae-mediated [198] African swine fever virus Asfarviridae CD163 Clathrin-mediated, Macropinocytosis [199] , [200] Ebolavirus Filoviridae DC-SIGN and other C-type lectin receptors Macropinocytosis [201] Vaccinia virus Poxviridae Heparan sulfate Proteoglycan Macropinocytosis [202] Human immunodeficiency virus-1 Retroviridae CD4 and CCR5or CXCR4 Clathrin-mediated Macropinocytosis [203] , [204] ...…”

“…Influenza A viruses utilize different endocytosis pathways for cell entry, depending on cell type: CME and dynamin-independent micropinocytosis [192] . The influenza A virus uses its major surface glycoprotein, hemagglutinin, to bind to different sialylated receptors on the host cell surface, including the sialic acid-containing, voltage-dependent Ca 2+ Cav1.2 channels [222] .…”

“…This causes fusion of the IAV membrane with the endosomal membrane. Subsequent virus uncoating releases the viral genome into the cytosol [192] . …”

Development and application of reverse genetic technology for the influenza virus

“…Therefore, new and more effective influenza vaccines are urgently required. The three common forms in global influenza vaccine development are inactivated influenza vaccines, recombinant influenza vaccines and live attenuated influenza vaccines [ 73 ]. The recombinant influenza virus constructed by plasmid-based reverse genetic technology is an important object in the research of recombinant influenza vaccines.…”

Influenza A (N1-N9) and Influenza B (B/Vic and B/Yam) Neuraminidase Pseudotypes as Tools for Pandemic Preparedness and Improved Influenza Vaccine design

“…Neuraminidase has been a successful target for antiviral drugs and is currently being studied as an alternative or adjunct to HA as a viable vaccine candidate with the potential to be employed as part of a ‘universal’ or ‘cross subtype’ influenza vaccine (18–20). The ultimate goal of a universal vaccine is to protect against infection from novel influenza viruses bearing combinations of H1-H18 and N1-N11.…”