Progresses on Studies of Highly Pathogenic Avian Influenza H5N1 Cross-Species Infection and its Pathogenesis

Review Article

Austin Virol and Retrovirology. 2014;1(1): 5.

Progresses on Studies of Highly Pathogenic Avian Influenza H5N1 Cross-Species Infection and its Pathogenesis

Rongbao Gao*

Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, China

*Corresponding author: Rongbao Gao, Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, CDC, 155 Changbai Rd, Changping District, Beijing 102206, China

Received: September 24, 2014; Accepted: November 13, 2014; Published: November 15, 2014


The threat posed by highly pathogenic avian influenza A (H5N1) viruses to humans remains significant since the virus has caused sporadic human infections in 16 countries with a high case fatality rate (approximately 60%), circulated in poultry in several countries, and has the potential possibility to induce pandemic by mutation or/and reassortment with other influenza A subtypes. Although many studies showed that a number of amino acid mutations may contribute the adaption, transmissibility or the pathogenicity of avian influenza A H5N1 virus in mammals, the mechanism of the cross-species transmission is not clear so far. The current evidences indicated that both the virus and infected host itself played key role on viral infection and the pathogenesis. Therefore, in addition to monitoring the virus activity and molecular changes, discovery on the pathway of host regulation and control linked to viral infection factors would be also very helpful to control and prevent the disease.

Keywords: Highly pathogenic avian influenza virus H5N1; Cross-species infection Pathogenesis


Highly Pathogenic Avian Influenza A Viruses (HPAIV) H5N1 have raised the global concerns due to high mortality and limited human-to-human transmission [1,2]. HPAIV H5N1 have spread and circulated in poultries in south east Asia, Europe and Africa since HPAIV H5N1 was first isolated from a farmed goose in Guangdong province of China in 1996 [3]. The virus caused first human infection in 1997 in Hongkong [4], reemerged in 2003, and had resulted into more than 650 human infections with almost 60% fatality in 16 countries since 2003 [5]. In addition, the virus showed to have potential droplet-transmissibility in humans by mutation or/ and reassortment [6-9]. However, there is not a very effective therapy policy for the disease with clinical feature of quick deterioration so far. Therefore, the threat posed by HPAIV H5N1 to humans remains significant. Here, we reviewed the risk of HPAIV H5N1 cross-species infection and its pathogenesis.

Cross-spices transmission in mammals

The “host species barrier” existing between avian species and humans was generally considered to restrict cross-species transmission of influenza virus. The successful trans-species transmission of avian influenza viruses and the establishment of adaption in the human population required to cross several barriers from their natural reservoirs to humans. These barriers can be divided along three major steps defining cross-species transmission [10]: (1) animal-to-human transmission barriers; (2) virus-cell interaction barriers; and (3) human-to-human transmission barriers.

Influenza virus preference of Sialic Acid (SA) linked to Galactose (Gal) receptors binding has purposed to be a key factor of animal-to-human transmission barriers. In general, human influenza viruses bind preferentially to SA linked to Gal by α-2, 6 linkage (SA α-2, 6-Gal), whereas avian influenza viruses bind preferentially to SA α-2, 3-Gal linkages, and pig influenza viruses either attached to both α2,3-SA and α2,6-SA, or exclusively to α2,6-SA [11]. The restriction present that the virus binds only to a species-specific cell receptor, or an efficient virus replication subject to cellular factors is prevented [12]. This is the primary reason that the avian influenza A virus cannot infect humans easily. However, the HPAIV H5N1 viruses have transmitted to infect humans and various mammals from poultry [4,13]. Animal surveillance data showed that HPAIV H5N1 had been detected in pig, dog, cat, leopard and tiger (Table 1). Genomic analysis showed that some of current circulating H5N1 viruses have presented changes of receptor-binding features such as capacity of human-like receptor- or double receptor-binding [14,15] and have multiple cell tropism [16]. To be different with seasonal influenza virus, HPAIV H5N1 can replicate with high-level in infected cells in vitro under the condition of no trypcin adjunction, and caused death of chick embro in just cultured 48h. Animal model studies showed that a low titer of virus may result into death of ferrets after infection [17] and the virus can infect and kill mice without any adaption which need be consulted in human viruses [18]. The virus has obvious lethality to guinea pig as well [19]. These studies indicated that the HPAIV H5N1 have been undergoing steps of cross-species transmission. Furthermore, the H5N1 HA gene mutation studies show that efficient droplet transmission can be induced in ferret infected by the A/Indonesia/5/2005 (H5N1) virus with two amino acid changes ( HA Q222L and G224S) on receptor binding sides and one mutation of HA T156A affecting on glycosylation N connection site [20] or virus with HA Q222L, N154D, T156A, T315I mutations of A/Vietnam/1203/2004 (H5N1) and remaining 7 H1N1pdm09 genes. These rescued viruses can bind both SA α-2,3 and α-2,6 Gal, and induced remarkable lung tissue damage and weight loss in ferrets [7]. These mutations in two (HA N154D/T156A) were common in H5N1 viruses circulating in poultry, indicating that it is possible to happen human-to-human transmission if these mutation or reassortments happened in nature. Fortunately, HPAIV H5N1 caused sporadic human infections only. Although the limited human-to-human transmission events have been reported in cluster cases from several countries [1, 21, 22] each reported cluster cases were from same family case yet. And no healthcare worker was transmitted to infect the virus so far [23].

Citation: Gao R. Progresses on Studies of Highly Pathogenic Avian Influenza H5N1 Cross-Species Infection and its Pathogenesis. Austin Virol and Retrovirology. 2014;1(1): 5. ISSN:2472-3517