Influenza virus is the causative agent of the seasonal and occasional pandemic flu.The current H1N1 influenza pandemic,announced by the WHO in June 2009,is highly contagious and responsible for global economic losses and fatalities.Although the H1N1 gene segments have three origins in terms of host species,the virus has been named swine-origin influenza virus(S-OIV)due to a predominant swine origin.2009 S-OIV has been shown to highly resemble the 1918 pandemic virus in many aspects.Hemagglutinin is responsible for the host range and receptor binding of the virus and is therefore a primary indicator for the potential of infection.Primary sequence analysis of the 2009 S-OIV hemagglutinin(HA)reveals its closest relationship to that of the 1918 pandemic influenza virus,however,analysis at the structural level is necessary to critically assess the functional significance.In this report,we report the crystal structure of soluble hemagglutinin H1(09H1)at 2.9Å,illustrating that the 09H1 is very similar to the 1918 pandemic HA(18H1)in overall structure and the structural modules,including the five defined antiboby(Ab)-binding epitopes.Our results provide an explanation as to why sera from the survivors of the 1918 pandemics can neutralize the 2009 S-OIV,and people born around the 1918 are resistant to the current pandemic,yet younger generations are more susceptible to the 2009 pandemic.
In March and early April 2009,a new swine-origin influenza A (H1N1) virus (S-OIV) emerged in Mexico and the United States. The virus spreads worldwide by human-to-human transmission.
Long-term endemicity of avian H5N1 influenza virus in poultry and continuous sporadic human infections in several countries has raised the concern of another potential pandemic influenza. Suspicion of the avian origin of the previous pandemics results in the close investigation of the mechanism of interspecies transmission. Entry and fusion is the first step for the H5N1 influenza virus to get into the host cells affecting the host ranges. Therefore receptor usage study has been a major focus for the last few years. We now know the difference of the sialic acid structures and distributions in different species, even in the different parts of the same host. Many host factors interacting with the influenza virus component proteins have been identified and their role in the host range expansion and interspecies transmission is under detailed scrutiny. Here we review current progress in the receptor usage and host factors.
Although worldwide concern has been raised since the large-scale outbreak of highly pathogenic avian influenza in wild birds at Qinghai Lake,China in 2005,the factors responsible for the ability to kill waterfowl remain unclear. The why and how questions of the H5N1 virus species-jump into its reservoir host need to be answered. In this report we test the pathogenicity and adaptation of Qinghai Lake (Clade 2.2) isolate to Muscovy ducks for further understanding of this virus. The isolate was highly pathogenic in ducks and retained its high pathogenicity even after 20 generations of passage in ducks. During the process of serial passages,only the NS gene developed non-synonymous substitutions,which caused two mutations in NS1 protein (Val23Ala and Leu207Pro) and one in NS2 (Phe55Leu). These mutations persisted immutably through all subsequent passages and the pathogenicity remained high,implying that highly pathogenic H5N1 virus remains stable in aquatic birds through oral transmission. Although the exact functions of these mutations are not known,our results provide an important foundation for further understanding the characteristics of the Qinghai Lake isolates.
PD-L1 is a member of the B7 protein family,most of whose members so far were identified as dimers in a solution and crystalline state,either complexed or uncomplexed with their ligand(s).The binding of PD-L1 with its receptor PD-1(CD279)delivers an inhibitory signal regulating the T cell function.Simultaneously with the Garboczi group,we successfully solved another structure of human PD-L1(hPD-L1).Our protein crystallized in the space group of C222_(1) with two hPD-L1 molecules per asymmetric unit.After comparison of reported B7 structures,we have found some intrinsic factors involved in the interaction of these two molecules.Based on these results,we tend to believe this uncomplexed hPD-L1 structure demonstrated its potential dimeric state in solution,althougt it could just be an evolutionary relic,too weak to be detected under present technology,or still a functional unit deserved our attentions.
