Distinct glycoprotein inhibitors of influenza A virus in different animal sera.

Normal horse and guinea pig sera contain the glycoprotein inhibitor alpha 2-macroglobulin, which inhibits the infectivity and hemagglutinating activity of influenza A viruses of the H2 and H3 subtypes. In the current study, the presence of inhibitors of influenza A virus in pig and rabbit sera was investigated. Variants of influenza virus type A/Los Angeles/2/87(H3N2) that were resistant to horse, pig, or rabbit serum were isolated. Analysis of the variant viruses with anti-hemagglutinin (HA) monoclonal antibodies revealed that antigenic changes occurred with the development of serum inhibitor resistance. Characterization of the inhibitors in pig and rabbit sera by using periodate and receptor-destroying enzyme demonstrated that carbohydrate is an important constituent of the active portion of both inhibitor molecules and that sialic acid is involved in the interaction of the inhibitors with influenza virus HA. Nucleotide sequence analysis of the HA molecule revealed that the serum-resistant variants each acquired a different set of amino acid alterations. The multiply resistant variants maintained the original amino acid changes and acquired additional changes. Sequence modifications in the HA involved the conserved amino acids within the receptor binding site (RBS) at position 137 and the second-shell RBS residues at positions 155 and 186. Amino acid changes also occurred within antigenic site A (position 145) and directly behind the receptor binding pocket (position 220). Amino acid alterations resulted in the acquisition of a potential glycosylation site at position 128 and the loss of potential glycosylation sites at positions 246 and 248. The localization of the amino acid changes in HA1 to the region of the RBS supports the concept of serum inhibitors as receptor analogs. The unique set of mutations acquired by the serum inhibitor-resistant variants strongly suggests that horse, pig, and rabbit sera each contain distinct glycoprotein inhibitors of influenza A virus.     

山东地区16株H9N2亚型禽流感病毒HA基因的序列分析

为了解H9N2亚型禽流感病毒(AIV)山东分离株的遗传变异情况,采用RT-PCR技术对16株从山东不同地区分离的H9N2亚型禽流感病毒的HA基因进行扩增、克隆和测序,并对所获得的HA全序列进行同源性和遗传进化分析。结果显示,16个分离株的裂解位点均为RSSR↓GLF,符合低致病性禽流感病毒的分子特征;有7～9个潜在糖基化位点;受体结合位点除198位有变异,其他位点均较保守;234位氨基酸均为L,具有与哺乳动物唾液酸α,2-6受体结合的特征;16个分离株HA基因核苷酸及氨基酸序列同源性分别为96.3%～99.9%和97.1%～99.6%;16个分离株同属于欧亚分支中的A/Duck/Hong Kong/Y280/97亚群。     

南京市2011年乙型流感血凝素基因分子特征分析

[目的]分析2011年南京市乙型流感病毒的血凝素(HA)分子学特征.[方法]选择7株2011年南京市不同时间段有代表性的乙型流感毒株进行HA基因序列测定,通过生物信息学方法对HA分子学特征进行分析.[结果]7株乙型流感毒株分为两个系,4株为Victoria,3株为Yamagata;与2011年度疫苗株相比,Victoria和Yamagata系毒株分别在抗原位点146、197和116、198发生了氨基酸替换;其中197和198位点分别是Victoria和Yamagata毒株的受体结合位点,由于上述位点的替换使得Victoria系/Yamagata系毒株分别在197/196位增加了一个潜在的糖基化位点.[结论]2011年南京市乙型流感Victoria 系和Yamagata系病毒同时存在,Victoria/Yamagata毒株197/198位点的氨基酸替换,值得做进一步的探讨.     

The hemagglutinins of duck and human H1 influenza viruses differ in sequence conservation and in glycosylation.

We determined the deduced amino acid sequences of two H1 duck influenza A virus hemagglutinins (HAs) and found that the consensus sequence of the HA, determined directly from virus recovered from the intestinal tract, remains unchanged through many generations of growth in MDCK cells and chicken embryos. These two duck viruses differ from each other by 5 amino acids and from A/Dk/Alberta/35/1976 (F. J. Austin, Y. Kawaoka, and R. G. Webster, J. Gen. Virol. 71:2471-2474, 1990) by 9 and 12 amino acids, most of which are in the HA1 subunit. They are antigenically similar to each other but different from the Alberta virus. We compared these H1 duck HAs with the HAs of human isolates to identify structural properties of this viral glycoprotein that are associated with host range. By comparison to the human H1 HAs, the duck virus HA sequences are highly conserved as judged by the small fraction of nucleotide differences between strains which result in amino acid substitutions. However, the most striking difference between these duck and human HAs is in the number and distribution of glycosylation sites. Whereas duck and swine viruses have four and five conserved glycosylation sites per HA1 subunit, none of which are on the tip of the HA, all human viruses have at least four additional sites, two or more of which are on the tip of the HA. These findings stress the role of glycosylation in the control of host range and suggest that oligosaccharides on the tip of the HA are important to the survival of H1 viruses in humans but not in ducks or swine.     

我国部分地区H9亚型禽流感病毒血凝素基因序列比较与遗传发生关系分析

为从分子水平掌握我国H9亚型AIV的遗传变异情况和流行规律,本研究汇集近年来从我国12个省、市、自治区的发病鸡群中分离到的23株H9亚型禽流感病毒,通过RT-PCR方法和核苷酸序列测定获得了23个毒株的HA基因cDNA核苷酸序列。核苷酸和推导的氨基酸序列同源性比较结果表明,这些毒株HA基因的核苷酸序列同源性为94．1％～100％,氨基酸序列同源性为95．4％～100%;将这23个毒株和来自亚洲及世界其它地区的另外31株的HA基因cDNA序列同源性进行比较发现,分离自香港的HK170499株与日本的2个毒株关系较近;氨基酸序列分析发现,CKGS199、CKTJ196、CKTJ296、CKSH300和CKBJ197五个毒株各发生了一个潜在的糖基化位点的丢失。54株H9亚型AIVHA基因55bp～1152bp的氨基酸序列分析发现,裂解位点尽管有10种基序,但本研究中的23株和近年来从我国大陆和香港地区的分离的毒株则均为RSSR↓GLF;构成受体结合位点的191位氨基酸有一个规律,即所有中国大陆毒株与部分香港毒株都为N,其它毒株均为H,141aa～143aa处的糖基化位点有与191aa类似的规律,即：凡是191aa为N的毒株,该处均为NVS（CKBJ194除外）,凡是191aa为H的毒株,则该处均为NVT;遗传发生关系分析,中国大陆毒株处于欧亚谱系的第一支。本研究结果表明近年来我国鸡群中H9N2亚型禽流感病毒的感染流行可能有一个共同的来源,这为制定防治该亚型禽流感流行的有效对策提供了重要的科学依据。     

Glycosylation site alteration in the evolution of influenza A (H1N1) viruses

Influenza virus typically alters protein glycosylation in order to escape immune pressure from hosts and hence to facilitate survival in different host environments. In this study, the patterns and conservation of glycosylation sites on HA and NA of influenza A/H1N1 viruses isolated from various hosts at different time periods were systematically analyzed, by employing a new strategy combining genome-based glycosylation site prediction and 3D modeling of glycoprotein structures, for elucidation of the modes and laws of glycosylation site alteration in the evolution of influenza A/H1N1 viruses. The results showed that influenza H1N1 viruses underwent different alterations of protein glycosylation in different hosts. Two alternative modes of glycosylation site alteration were involved in the evolution of human influenza virus: One was an increase in glycosylation site numbers, which mainly occurred with high frequency in the early stages of evolution. The other was a change in the positional conversion of the glycosylation sites, which was the dominating mode with relatively low frequency in the later evolutionary stages. The mechanisms and possibly biological functions of glycosylation site alteration for the evolution of influenza A/H1N1 viruses were also discussed. Importantly, the significant role of positional alteration of glycosylation sites in the host adaptation of influenza virus was elucidated. Although the results still need to be supported by experimental data, the information here may provide some constructive suggestions for research into the glycosylation of influenza viruses as well as even the design of surveillance and the production of viral vaccines.     

Antigenic structure of the influenza B virus hemagglutinin: nucleotide sequence analysis of antigenic variants selected with monoclonal antibodies.

We report here the complete nucleotide sequence of the hemagglutinin (HA) gene of influenza B virus B/Oregon/5/80 and, through comparative sequence analysis, identify amino acid substitutions in the HA1 polypeptide responsible for the antigenic alterations in laboratory-selected antigenic variants of this virus. The complete nucleotide sequence of the B/Oregon/5/80 HA gene was established by a combination of chemical sequencing of a full-length cDNA clone and dideoxy sequencing of the virion RNA. The nucleotide sequence is very similar to previously reported influenza B virus HA gene sequences and differs at only nine nucleotide positions from the B/Singapore/222/79 HA gene (Verhoeyen et al., Nucleic Acids Res. 11:4703-4712, 1983). The nucleotide sequences of the HA1 portions of the HA genes of 18 laboratory-selected antigenic variants were determined by the dideoxy method. Comparison of the deduced amino acid sequences of the parental and variant HA1 polypeptides revealed 16 different amino acid substitutions at nine positions. All amino acid substitutions resulted from single-point mutations, and no double mutants were detected, demonstrating that as in the influenza A viruses, single amino acid substitutions are sufficient to alter the antigenicity of the HA molecule. Many of the amino acid substitutions in the variants occurred at positions also observed to change in natural drift strains. The substitutions appear to identify at least two immunodominant regions which correspond to proposed antigenic sites A and B on the influenza A virus H3 HA.     

Mutational analysis of conserved N-linked glycosylation sites of human immunodeficiency virus type 1 gp41.

Amino acid substitutions were introduced into four conserved N-linked glycosylation sites of the human immunodeficiency virus type 1 envelope transmembrane glycoprotein, gp41, to alter the canonical N-linked glycosylation sequences. One altered site produced a severe impairment of viral infectivity, which raises the possibility that N-linked sugars at this site may have an important role in the human immunodeficiency virus type 1 life cycle.     

Evolutionary pattern of the hemagglutinin gene of influenza B viruses isolated in Japan: cocirculating lineages in the same epidemic season.

The unexpectedly low efficacy of influenza vaccine during school outbreaks of influenza B virus in the spring of 1987 in Japan was probably attributable to a poor antibody response of vaccinees to the epidemic viruses. An antigenic analysis of the causative B viruses isolated in 1987 and 1988 showed much variation in hemagglutination inhibition patterns. The nucleotide sequences that code for the HA1 domain of B/Fukuoka/c-27/81, B/Ibaraki/2/85, B/Nagasaki/1/87, and B/Yamagata/16/88 viruses were determined and compared with those of the previously reported hemagglutinin genes. The nucleotide sequences of the hemagglutinin gene of a new variant, B/Yamagata/16/88, had only 93.4% homology with those of two other viruses from the same epidemic. An analysis of nucleotide and amino acid substitutions of the hemagglutinin genes of influenza B viruses revealed that new and some old variants could cocirculate in the same epidemic. A phylogenetic tree constructed by the neighbor-joining method allowed estimation of an evolutionary rate of 2.3 x 10(-3) synonymous (silent) substitutions per nucleotide site per year in the hemagglutinin gene.     

2017–2019年我国南方地区高致病性H5N6亚型禽流感病毒血凝素蛋白分子特征分析

【背景】自2014年以来,H5N6禽流感病毒在我国家禽和活禽市场持续进化,成为人类和动物健康的重大威胁。【目的】对2017-2019年中国南方地区93株高致病性H5N6禽流感病毒的HA基因进行分子进化分析。【方法】接种9-11日龄鸡胚分离核酸检测阳性的H5N6标本,运用下一代测序平台对病毒分离物进行全基因组测序,从NCBI和GISAID数据库下载参考序列,利用BLAST、MEGA6.1及Clustal X等软件进行序列分析。【结果】2017-2019年,从189份江苏省H5亚型禽类/环境标本和1名H5N6患者咽拭子标本中共分离到43株病毒,完成了33株H5N6病毒的全基因组测序。下载网上同时期中国其他地区流行的H5N6毒株序列,对总计93株H5N6病毒的HA基因进行分子进化分析。93株H5N6病毒中有78株属于Clade 2.3.4.4h,9株病毒属于Clade 2.3.4.4e,4株H5N6病毒属于Clade 2.3.4.4b,1株属于Clade 2.3.4.4f,1株属于Clade 2.3.4.4g。所有93株病毒HA蛋白的裂解位点含有多个碱性氨基酸,表明它们都属于高致病性禽流感病毒。所有93株病毒HA蛋白的Q222和G224位氨基酸没有发生突变,保留了禽类受体α2-3半乳糖苷唾液酸(SAα2-3Gal)结合特性;158位点丧失糖基化,同时124位出现一个新的潜在糖基化位点。【结论】2017-2019年间中国南方地区H5N6病毒进化活跃,具有明显的基因多样性,需要加强对病毒分子进化的监测。     

长沙A(H1N1)亚型季节性流感暴发疫情的实验室诊断及其HA基因特性分析

对2009 年长沙麓山国际学校流感暴发疫情进行实验室诊断, 并探索新分离的A(H1N1)亚型流感病毒血凝素(HA)的基因特性。对流感暴发疫情的25 份鼻/咽拭子标本进行RT-PCR检测和流感病毒分离, 然后利用CEQ?8000 Genetic Analysis System对病毒分离株(A/Yuelu/314/2009)进行测序, 测序结果提交至GenBank(登录号: FJ912843)并用ClustalX和Mega4.1软件进行序列分析。结果显示, 分离出A(H1N1)亚型流感毒株18株, 检出21份A(H1N1)亚型流感病毒核酸阳性; A/Yuelu/314/2009(H1N1) HA基因序列与2008~2009 年疫苗株(A/Brisbane/59/2007)比较显示: 核苷酸和氨基酸同源性均为99%, 有6个位点的氨基酸发生了变异(V148A、S158N、G202A、I203D、A206T、W435R), 其中一个S158N氨基酸变异位于B抗原表位, HA基因序列上共有潜在糖基化位点9 个(27、28、40、71、151、176、303、497、536), 与A/Brisbane/59/2007相同且氨基酸序列保守。本实验诊断出此次流感暴发疫情的病原体为A(H1N1)型季节性流感病毒, 研究还发现A/Yuelu/314/2009(H1N1)长沙分离株与A/Brisbane/59/2007 疫苗株基因序列比较显示并未形成一个新的变种, 推测是由于分离株与疫苗株之间基因特性的改变和人群对A(H1N1)亚型流感病毒免疫力降低导致了此次长沙麓山国际学校A(H1N1)亚型流感的暴发。     

N-linked glycosylation of the HIV type-1 gp120 envelope glycoprotein as a major determinant of CCR5 and CXCR4 coreceptor utilization

The variable V1V2 and V3 regions of the human immunodeficiency virus type-1 (HIV-1) envelope glycoprotein (gp120) can influence viral coreceptor usage. To substantiate this we generated isogenic HIV-1 molecularly cloned viruses that were composed of the HxB2 envelope backbone containing the V1V2 and V3 regions from viruses isolated from a patient progressing to disease. We show that the V3 amino acid charge per se had little influence on altering the virus coreceptor phenotype. The V1V2 region and its N-linked glycosylation degree were shown to confer CXCR4 usage and provide the virus with rapid replication kinetics. Loss of an N-linked glycosylation site within the V3 region had a major influence on the virus switching from the R5 to X4 phenotype in a V3 charge-dependent manner. The loss of this V3 N-linked glycosylation site was also linked with the broadening of the coreceptor repertoire to incorporate CCR3. By comparing the amino acid sequences of primary HIV-1 isolates, we identified a strong association between high V3 charge and the loss of this V3 N-linked glycosylation site. These results demonstrate that the N-linked glycosylation pattern of the HIV-1 envelope can strongly influence viral coreceptor utilization and the R5 to X4 switch.     

Studies on the adaptation of influenza viruses to MDCK cells

The amino acid sequences and biological properties of the haemagglutinin of three variants of the influenza virus X-31 (H3N2) selected for their capacity to grow in MDCK cells are reported. In two variants, amino acid substitutions at HA1 residues 8 and 144 correlated with the loss of a site for glycosylation and specific changes in antigenicity, respectively. In all three variants substitution of an arginine residue for histidine at HA1 position 17 was correlated with increased pH optima of haemolysis. The importance of this substitution for cleavage of the haemagglutinin precursor required to produce infectious virus is discussed in relation to the three-dimensional structure of X-31 haemagglutinin.     

Alterations in receptor binding properties of recent human influenza H3N2 viruses are associated with reduced natural killer cell lysis of infected cells

Natural killer (NK) cell recognition of influenza virus-infected cells involves hemagglutinin (HA) binding to sialic acid (SA) on activating NK receptors. SA also acts as a receptor for the binding of influenza virus to its target host cells. The SA binding properties of H3N2 influenza viruses have been observed to change during circulation in humans: recent isolates are unable to agglutinate chicken red blood cells and show reduced affinity for synthetic glycopolymers representing SA-alpha-2,3-lactose (3'SL-PAA) and SA-alpha-2,6-N-acetyl lactosamine (6'SLN-PAA) carbohydrates. Here, NK lysis of cells infected with human H3N2 influenza viruses isolated between 1969 and 2003 was analyzed. Cells infected with recent isolates (1999 to 2003) were found to be lysed less effectively than cells infected with older isolates (1969 to 1996). This change occurred concurrently with the acquisition of two new potential glycosylation site motifs in HA. Deletion of the potential glycosylation site motif at 133 to 135 in HA1 from a recent isolate partially restored the agglutination phenotype to a recombinant virus, indicating that the HA-SA interaction is inhibited by the glycosylation modification. Deletion of either of the recently acquired potential glycosylation sites from HA led to increased NK lysis of cells infected with recombinant viruses carrying modified HA. These results indicate that alterations in HA glycosylation may affect NK cell recognition of influenza virus-infected cells in addition to virus binding to host cells.     

Molecular determinants within the surface proteins involved in the pathogenicity of H5N1 influenza viruses in chickens

Although it is established that the cleavage site and glycosylation patterns in the hemagglutinin (HA) play important roles in determining the pathogenicity of H5 avian influenza viruses, some viruses exist that are not highly pathogenic despite possessing the known characteristics of high pathogenicity (i.e., their HA contains multiple basic amino acids at the cleavage site and has glycosylation patterns similar to that of the highly pathogenic H5 viruses). Currently little is known about the H5N1 viruses that fall into this intermediate category of pathogenicity. We have identified strains of H5N1 avian influenza viruses that have markers typical of high pathogenicity but distinctly differ in their ability to cause disease and death in chickens. By analyzing viruses constructed by reverse-genetic methods and containing recombinant HAs, we established that amino acids 97, 108, 126, 138, 212, and 217 of HA, in addition to those within the cleavage site, affect pathogenicity. Further investigation revealed that an additional glycosylation site within the neuraminidase (NA) protein globular head contributed to the high virulence of the H5N1 virus. Our findings are in agreement with previous observations that suggest that the activities of the HA and NA proteins are functionally linked.     

Hemagglutinin mutations related to antigenic variation in H1 swine influenza viruses.

The hemagglutinin (HA) of a recent swine influenza virus, A/Sw/IN/1726/88 (H1N1), was shown previously to have four antigenic sites, as determined from analysis of monoclonal antibody (MAb)-selected escape mutants. To define the HA mutations related to these antigenic sites, we cloned and sequenced the HA genes amplified by polymerase chain reaction of parent virus and MAb-selected escape mutants. The genetic data indicated the presence of four amino acid changes. After alignment with the three-dimensional structure of H3 HA, three changes were located on the distal tip of the HA, and the fourth was located within the loop on the HA. We then compared our antigenic sites, as defined by the changed amino acids, with the well-defined sites on the H1 HA of A/PR/8/34. The four amino acid residues corresponded with three antigenic sites on the HA of A/PR/8/34. This finding, in conjunction with our previous antigenic data, indicated that two of the four antigenic sites were overlapping. In addition, our previous studies indicated that one MAb-selected mutant and a recent, naturally occurring swine isolate reacted similarly with the MAb panel. However, their amino acid changes were different and also distant on the primary sequence but close topographically. This finding indicates that changes outside the antigenic site may also affect the site. A comparison of the HA amino acid sequences of early and recent swine isolates showed striking conservation of genetic sequences as well as of the antigenic sites. Thus, swine influenza viruses evolve more slowly than human viruses, possibly because they are not subjected to the same degree of immune selection.     

Emergence and genetic variation of neuraminidase stalk deletions in avian influenza viruses

When avian influenza viruses (AIVs) are transmitted from their reservoir hosts (wild waterfowl and shorebirds) to domestic bird species, they undergo genetic changes that have been linked to higher virulence and broader host range. Common genetic AIV modifications in viral proteins of poultry isolates are deletions in the stalk region of the neuraminidase (NA) and additions of glycosylation sites on the hemagglutinin (HA). Even though these NA deletion mutations occur in several AIV subtypes, they have not been analyzed comprehensively. In this study, 4,920 NA nucleotide sequences, 5,596 HA nucleotide and 4,702 HA amino acid sequences were analyzed to elucidate the widespread emergence of NA stalk deletions in gallinaceous hosts, the genetic polymorphism of the deletion patterns and association between the stalk deletions in NA and amino acid variants in HA. Forty-seven different NA stalk deletion patterns were identified in six NA subtypes, N1-N3 and N5-N7. An analysis that controlled for phylogenetic dependence due to shared ancestry showed that NA stalk deletions are statistically correlated with gallinaceous hosts and certain amino acid features on the HA protein. Those HA features included five glycosylation sites, one insertion and one deletion. The correlations between NA stalk deletions and HA features are HA-NA-subtype-specific. Our results demonstrate that stalk deletions in the NA proteins of AIV are relatively common. Understanding the NA stalk deletion and related HA features may be important for vaccine and drug development and could be useful in establishing effective early detection and warning systems for the poultry industry.     

Genetic diversity of the 2009 pandemic influenza A(H1N1) viruses in Finland

Background

In Finland, the first infections caused by the 2009 pandemic influenza A(H1N1) virus were identified on May 10. During the next three months almost all infections were found from patients who had recently traveled abroad. In September 2009 the pandemic virus started to spread in the general population, leading to localized outbreaks and peak epidemic activity was reached during weeks 43–48.

Methods/Results

The nucleotide sequences of the hemagglutinin (HA) and neuraminidase (NA) genes from viruses collected from 138 patients were determined. The analyzed viruses represented mild and severe infections and different geographic regions and time periods. Based on HA and NA gene sequences, the Finnish pandemic viruses clustered in four groups. Finnish epidemic viruses and A/California/07/2009 vaccine virus strain varied from 2–8 and 0–5 amino acids in HA and NA molecules, respectively, giving a respective maximal evolution speed of 1.4% and 1.1%. Most amino acid changes in HA and NA molecules accumulated on the surface of the molecule and were partly located in antigenic sites. Three severe infections were detected with a mutation at HA residue 222, in two viruses with a change D222G, and in one virus D222Y. Also viruses with change D222E were identified. All Finnish pandemic viruses were sensitive to oseltamivir having the amino acid histidine at residue 275 of the neuraminidase molecule.

Conclusions

The Finnish pandemic viruses were quite closely related to A/California/07/2009 vaccine virus. Neither in the HA nor in the NA were changes identified that may lead to the selection of a virus with increased epidemic potential or exceptionally high virulence. Continued laboratory-based surveillance of the 2009 pandemic influenza A(H1N1) is important in order to rapidly identify drug resistant viruses and/or virus variants with potential ability to cause severe forms of infection and an ability to circumvent vaccine-induced immunity.     

Rapid evolution of H5N1 influenza viruses in chickens in Hong Kong

The H5N1 avian influenza virus that killed 6 of 18 persons infected in Hong Kong in 1997 was transmitted directly from poultry to humans. Viral isolates from this outbreak may provide molecular clues to zoonotic transfer. Here we demonstrate that the H5N1 viruses circulating in poultry comprised two distinguishable phylogenetic lineages in all genes that were in very rapid evolution. When introduced into new hosts, influenza viruses usually undergo rapid alteration of their surface glycoproteins, especially in the hemagglutinin (HA). Surprisingly, these H5N1 isolates had a large proportion of amino acid changes in all gene products except in the HA. These viruses maybe reassortants each of whose HA gene is well adapted to domestic poultry while the rest of the genome arises from a different source. The consensus amino acid sequences of "internal" virion proteins reveal amino acids previously found in human strains. These human-specific amino acids may be important factors in zoonotic transmission.     

流感病毒识别糖链受体分子机制的研究进展

近年来,由于流感病毒(influenza virus)不可预测的局部流行和有可能引发全球大流行,其一直是研究的热点课题之一．流感病毒表面糖蛋白血凝素(hemagglutinin,HA)特异识别宿主细胞表面的糖链受体是流感病毒感染宿主、进而复制并继续传播的生物学基础．影响流感病毒宿主特异性的两个主要因素是HA自身的变化(包括基因突变、重组、糖基化位点数量和糖基化位置的变化)和宿主细胞表面糖链受体的变化(包括糖链受体的类型、分布和分子构象的改变)等．因此准确掌握这些信息有助于人们进一步加强对流感病毒的防控．本文主要从糖组学角度概述了流感病毒识别糖链受体的分子机制,重点介绍流感病毒宿主细胞表面糖链受体的研究进展．