Viral tropism is a cornerstone in the spread and spillover of avian influenza viruses

Abstract

In recent years, high pathogenicity avian influenza viruses (HPAIVs) have spread among wild, captive, and domestic birds, as well as mammals. Beyond the resulting economic and ecological losses, spillover into mammals has raised concerns about a potential pandemic. Viral tropism refers to the spectrum of host species, organs, and cells susceptible and permissive to viral infection. It is a potent driver of infection dynamics and shedding patterns, which presents important variations both between and within hosts: in poultry, HPAIV leads to systemic endothelial infection in domestic chickens, whereas neurological and selective epithelial infections are observed in domestic ducks. In mammals, infection can result in respiratory and neurological disease, but the recent outbreaks in domestic dairy cows highlighted a unique and remarkable adaptation to the mammary gland prone to viral shedding in milk. The present review explores viral tropism of HPAIV across recent spillover from birds to mammals and discusses its critical involvement in viral ecology, requiring the constant surveillance and adaptation of control measures.

Keywords: avian influenza; host adaptation; pathogenesis; viral tropism.

Fig 1

Selective and host-dependent tissue tropism of H5 HPAIVs from birds to mammals. Organs highlighted in red indicate sites of active viral replication and associated lesions. (1) In domestic Anseriformes, such as ducks, Gs/Gd H5 HPAI infection leads to systemic infection that can progress to neurological disease over the course of infection. Tissue pantropism is selective, including marked neurotropism, visceral tropism, and feather epitheliotropism. The infection course in chickens is shorter due to prominent systemic endotheliotropism resulting in systemic fatal acute disease and widespread viral replication. In addition, wild waterbirds carry and spread Gs/Gd H5 HPAIVs, with variable clinical outcomes ranging from asymptomatic to death. (2) In domestic dairy cows, H5 HPAIV presents a remarkable selective tropism for mammary epithelium leading to diffusion into milk. In carnivorous terrestrial (3) and marine (4) mammals, infection is characterized by a marked tropism for respiratory and nervous tissues. (5) In humans, localized forms of Gs/Gd H5 HPAI infection include conjunctivitis as reported in the dairy cow outbreaks in the United States, while severe forms were associated with prominent respiratory tropism and sometimes neurotropism.