A review of H5Nx avian influenza viruses

Abstract

Highly pathogenic avian influenza viruses (HPAIVs), originating from the A/goose/Guangdong/1/1996 H5 subtype, naturally circulate in wild-bird populations, particularly waterfowl, and often spill over to infect domestic poultry. Occasionally, humans are infected with HPAVI H5N1 resulting in high mortality, but no sustained human-to-human transmission. In this review, the replication cycle, pathogenicity, evolution, spread, and transmission of HPAIVs of H5Nx subtypes, along with the host immune responses to Highly Pathogenic Avian Influenza Virus (HPAIV) infection and potential vaccination, are discussed. In addition, the potential mechanisms for Highly Pathogenic Avian Influenza Virus (HPAIV) H5 Reassorted Viruses H5N1, H5N2, H5N6, H5N8 (H5Nx) viruses to transmit, infect, and adapt to the human host are reviewed.

Keywords: H5N1; H5Nx in humans; H5Nx viruses; avian influenza; avian influenza in swine; avian influenza outbreaks; evolution of H5Nx; highly pathogenic avian influenza; influenza replication; zoonotic diseases.

Figure 1.

Cartoon depiction of the replication cycle of influenza viruses. (Step 1) Viral entry into host cell. (Step 2) Virus endocytosis into host endosome and acidification, leading to conformational change of the HA molecule exposing fusion peptide and fusion of viral and host membrane. M2 protein pumps H+ atoms into the viral core, causing the dissociation of M1 and the release of vRNP. (Step 3) Release of vRNP into the cytoplasm and translocation into the nucleus. (Step 4) vRNP replication and transcription, and cap-snatching mechanisms occur in the nucleus. Viral proteins such as M1 and NS2 chaperone vRNP out of the nucleus and into the cytoplasm to be packaged into viral particles. (Step 5) Structural proteins are translated by host ribosomes and are transported to the endoplasmic reticulum for proper folding. (Step 6) Properly folded viral proteins are released from the endoplasmic reticulum and are directed towards the plasma membrane or to the Golgi for modifications prior to release. (Step 7) Movement of modified proteins from the Golgi network to the plasma membrane for viral budding. (Step 8) Release of infectious viral progeny.

Figure 2.

Depiction of swine reassortants. Seasonal influenza from human hosts (left) can be transmitted into susceptible swine. Concurrent infection by avian strains (H5Nx) with seasonal influenza strains can lead to reassortants, novel influenza viruses that contain genetic segments from both humans and avian viruses. These novel viruses can then be transmitted into susceptible human populations, possibily leading to a pandemic outbreak. Human outline: by Linda Salzman Sagan (original artwork); Tompw (GIF version); User:Holek (SVG) – Cut from File:Pioneer10-plaque.jpg, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=2647647.