Evolutionary dynamics of highly pathogenic avian influenza A/H5N1 HA clades and vaccine implementation in Vietnam

Abstract

Based on hemagglutinin (HA) and neuraminidase (NA), influenza A virus is divided into 18 different HA (H1 to H18) and 11 NA types (N1 to N11), opening the possibility for reassortment between the HA and NA genes to generate new HxNy subtypes (where x could be any HA and y is any NA, possibly). In recent four years, since 2010, highly pathogenic avian influenza (HPAI) viruses of H5N1 subtype (HPAI A/H5N1) have become highly enzootic and dynamically evolved to form multiple H5 HA clades, particularly in China, Vietnam, Indonesia, Egypt, Cambodia, and Bangladesh. So far, after more than 10 years emerged in Vietnam (since late 2003), HPAI A/H5N1 is still posing a potential risk of causing outbreaks in poultry, with high frequency of annual endemics. Intragenic variation (referred to as antigenic drift) in HA (e.g., H5) has given rise to form numerous clades, typically marking the major timelines of the evolutionary status and vaccine application in each period. The dominance of genetically and antigenically diversified clade 2.3.2.1 (of subgroups a, b, c), clade 1.1 (1.1.1/1.1.2) and re-emergence of clade 7.1/7.2 at present, has urged Vietnam to the need for dynamically applied antigenicity-matching vaccines, i.e., the plan of importing Re-6 vaccine for use in 2014, in parallel use of Re-1/Re-5 since 2006. In this review, we summarize evolutionary features of HPAI A/H5N1 viruses and clade formation during recent 10 years (2004-2014). Dynamic of vaccine implementation in Vienam is also remarked.

Keywords: Clades; Genotypes; HPAI A/H5N1; Orthomyxoviridae; Reassortment; Subtypes; Vaccines; Vietnam.

Fig. 1

Emergence timelines of hemagglutinin-based clades of A/H5N1 in Vietnam (only those clades that emerged and identified in Vietnam are presented). Data used for making timelines of H5N1 occurence were collected from the following published sources: Nguyen et al. [41,42], Creanga et al. [43], World Health Organization/World Organisation for Animal Health/Food and Agriculture Organization (WHO/OIE/FAO) H5N1 Evolution Working Group [44], Inui [45]; A/B/C marks for clades were taken from the above listed publications; question mark (?) indicates upcoming confirmation of clades in 2014.

Fig. 2

Phylogenetic tree based on the hemagglutinin H5 sequences (1,588 nucleotides) of representative A/H5N1 viruses including those of predominant clades in Vietnam since 2004. Topology was constructed by MEGA6.06 using the neighbor-joining analysis of the boostrap method with 1,000 replications (values <40 were not shown) [72]. Clades were nomenclatured based on the criteria and the reference strains determined in World Health Organization (WHO)/World Organisation for Animal Health (OIE)/Food and Agriculture Organization of the United Nations (FAO)-2014 system [44]. Major clades of H5N1 are shown as groups of monophyletic branches. Regarding to clade 2.3.2.1, viruses are divided into clade 2.3.2.1a (A/Hubei/1/2010-like); 2.3.2.1b (A/barn-swallow/Hong Kong/1161/2010-like); and 2.3.2.1c (A/Hong Kong/6841/2010-like). Note: Clades/subclades for prototype reference strains are bolded and parenthesized for indication. VN, Vietnam; HK, Hong Kong; KR, South Korea; KH, Cambodia. ^a)Viruses from our own study, marked at end of each strain. Scale bar at bottom indicates the number of nucleotide substitutions per site; the corresponding GenBank accession number are denoted at end of each sequence where applicable.