Family Clustering of Avian Influenza A (H5N1)

What is the evidence of a role for host genetics in susceptibility to influenza A/H5N1?

“…Familial aggregation of cases Between 1 January 1997 and 25 November 2009 a total of 36 clusters of two or more laboratoryconfirmed cases of A/H5N1 have been reported, with at least an additional 16 clusters of one confirmed case plus at least one probable case [3,4,[8][9][10][11] (Table 1). These 52 clusters account for 22 % (103/463) of all laboratory-confirmed cases and only six of the 103 cases occurring in clusters did not have a genetic relationship to another case in the cluster.…”

“…The role of cell surface sialic acid receptors in the determination of host specificity of influenza viruses is well documented and therefore the genes encoding these receptors and their associated glycan modifications are potential candidates [55][56][57][58]. Cytokine dysregulation has been shown to be a feature of A/H5N1 infection in clinical and animal studies [59][60][61] and various aspects of innate immunity including collectin-like mannose-binding lectin, tolllike receptors (TLR 3,7,8), cytokines, chemokines, and interferon-inducible proteins such as MxA are also plausible candidates [62][63][64][65][66][67][68]. Interestingly, susceptibility to other viral respiratory pathogens has been traced to genes of the innate immune system [69][70][71][72][73].…”

Lack of transmission of H5N1 avian–human reassortant influenza viruses in a ferret model

“…Since 1997, when HPAI H5N1 viruses first emerged in Hong Kong to cause human respiratory illness and death, Ͼ200 laboratory-confirmed human infections have been reported, primarily as a result of transmission of the H5N1 virus from domestic poultry to humans (1)(2)(3)(4). Despite limited instances of probable human-to-human transmission (5,6), H5N1 viruses have not yet acquired the ability to transmit efficiently among humans. The viral properties that confer transmissibility of influenza viruses among humans, and mammalian species in general, remains poorly understood, yet are clearly key factors that determine whether a novel subtype introduced into an immunologically naïve human population will result in a pandemic.…”

“…In contrast, the H2N2 and H3N2 viruses that caused pandemics in 1957 and 1968, respectively, were the result of reassortment between avian and human influenza A viruses, acquiring the neuraminidase (NA) and͞or hemagglutinin (HA), and PB1 gene from an avian virus and other genes from the previously circulating human strain (9). However, the earliest human H2 and H3 isolates differed from their avian counterparts in key receptor-binding residues that resulted in preferred binding of the human virus HA to sialic acid (SA) ␣2, 6 receptors, suggesting that a shift from avian virus SA ␣2,3 to human virus SA ␣2,6 receptor-binding specificity is critical for efficient replication and spread of a pandemic strain (10). H5N1 viruses isolated from humans to date possess all eight gene segments that are entirely avian in origin, and with only a few exceptions, have retained a receptor-binding site sequence in the HA that is typical of the avian virus preference for binding SA ␣2, 3 (11-13).…”

Two clustered cases of confirmed influenza A(H5N1) virus infection, Cambodia, 2011

“…Clusters of confirmed human cases have been described in the past in Azerbaijan [2], mainland China [3], Egypt [4], Hong Kong [5], Indonesia [6], Pakistan [7,8] Thailand [9], Turkey [10] and Vietnam [11]. In at least one Indonesian cluster, transmission of A(H5N1) may have occurred through contact with environmentally-contaminated material [12].…”