Modeling and analyzing self-resistance of connected automated vehicular platoons under different cyberattack injection modes.

The high-level integration and interaction between the information flow at the cyber layer and the physical subjects at the vehicular layer enables the connected automated vehicles (CAVs) to achieve rapid, cooperative and shared travel. However, the cyber layer is challenged by malicious attacks and the shortage of communication resources, which makes the vehicular layer suffer from system nonlinearity, disturbance randomness and behavior uncertainty, thus interfering with the stable operation of the platoon. So far, scholars usually adopt the method of assuming or improving the car-following model to explore the platoon behavior and the defense mechanism in cyberattacks, but they have not considered whether the model itself has disturbance and impact on cyberattack defenses. In other words, it is still being determined whether the car-following model designed can be fully applicable to such cyberattacks. To provide a theoretical basis for vehicular layer modeling, it is necessary to comprehend the self-resistance of different car-following models faced on various cyberattacks. First, we review the car-following models adopted on the vehicular layer in cyberattacks, involving traffic engineering, physical statistics, and platoon dynamics. Based on the review, we divide the malicious attacks faced by the cyber layer into explicit attacks and implicit attacks. Second, we develop a cooperative generalized force model (CGFM), which combines and unifies the r-predecessors following communication topology. The proposed models, labeled the vulnerable cooperative intelligent driver model (VCIDM), the vulnerable cooperative optimal velocity model (VCOVM), and the vulnerable cooperative platoon dynamics model (VCPDM), incorporate the CGFM model and assorted cyberattack injection modes to explain the cyberattack effects on the platoon self-resistance capability. Upon the described models, we provide six indicators in three dimensions from the basic traffic element, including drivers, vehicles, and environment. These indicators illustrate driver tolerance, vehicle adaptability, and environmental resistance when a platoon faces attacks such as bogus information, replay/delay, and communication interruption. We arrange and reorganize the car-following models and the cyberattack injection modes to complete the research on the self-resistance capability of the platoon, which has positive research value and practical significance for enhancing the endogenous security at the vehicular layer and improving the intrusion tolerability at the cyber layer.

Recombinant influenza H1, H5 and H9 hemagglutinins containing replaced H3 hemagglutinin transmembrane domain showed enhanced heterosubtypic protection in mice.

Influenza A viruses cause annual epidemics and irregular pandemics. A vaccine with heterosubtypic protection (hetero-protection) has been needed. In the present study, various influenza H1, H3, H5, and H9 hemagglutinin (HA) proteins were expressed in insect cells, and then mice were subcutaneously immunized with the expressed HA proteins, and challenged by influenza A viruses (A/Puerto Rico/8/1934 (H1N1) or A/chicken/Guangdong/96 (H9N2)). The results first showed that wild-type H3 hemagglutinin (HA) (H3-WT), but not a transmembrane domain (TM) mutant, had hetero-protection against both H1N1 and H9N2 with survival rates of 17% and 33% respectively, and that wild-type H1 (H1-WT), H5 (H5-WT) and H9 (H9-WT) had no hetero-protection against H1N1 or H9N2 except for H5-WT against H1N1 with a survival rate of 17%. Then the H3-WT TM replaced the TMs of H1-WT, H5-WT and H9-WT to generate recombinant H1-TM, H5-TM and H9-TM respectively, and whether the H3-WT TM-dependent hetero-protection could be transferred to these TM mutants was investigated. The results showed that the H3-WT TM-dependent hetero-protection was transferable. H1-TM against H9N2 and H9-TM against H1N1 were with survival rates of 33% and 17% respectively, and H5-TM against both H1N1 and H9N2 with survival rates of 50% and 17% respectively. Furthermore, higher dosage H5-TM scored 100% hetero-protection against H1N1. These results demonstrated that replacement of the TMs of non-H3 HAs with H3-WT TM could enhance their hetero-protection. These findings would help the development of future influenza vaccines against pandemics such as the recently appeared H7N9 infection.

Evidences for the existence of intermolecular disulfide-bonded oligomers in the H3 hemagglutinins expressed in insect cells.

The hemagglutinin (HA) protein as the predominant antigen, executes receptor binding and membrane fusion, which critically influence the virological characteristics of influenza viruses. The literature contained scattered data showing reduction-sensitive HA oligomers when HA proteins were analyzed under non-reducing conditions. However, whether the reduction-sensitive HA oligomers are inter-monomer disulfide-bonded has not been studied. Here, we showed: (1) the detection of ß-mercaptoethanol-sensitive H3 HA oligomers was not affected by the treatment of cells with iodoacetamide prior to cell solubilization; (2) H3 HA oligomers were present on cell surfaces; (3) H3 HA oligomers had higher density than monomers; and (4) mutation of all the five C-terminal cysteines completely abolished the formation of H3 HA oligomers. Furthermore, mutant HAs with mutations of TM cysteines, CT cysteines or all five cysteines had decreased thermal stability but increased fusion activity in comparison with wildtype HA. In conclusion, this study has presented enough evidence for the existence of inter-monomer S-S H3 HA oligomers formed by five C-terminal cysteines, and suggested that all five C-terminal cysteines exerted opposite effects on HA thermal stability and fusion activity.

Mutations of two transmembrane cysteines of hemagglutinin (HA) from influenza A H3N2 virus affect HA thermal stability and fusion activity.

Influenza A H3N2 virus caused 1968 Hong Kong influenza pandemic, and has since been one of the most prevalent seasonal influenza viruses in global populations, representing a credible pandemic candidate in future. Previous studies have established that the hemagglutinin (HA) protein is the predominant antigen and executes receptor binding and membrane fusion. Homologous sequence analysis of all HA subtypes of influenza viruses revealed that two cysteine residues (540 and 544) are uniquely present in the transmembrane domain (TM) of HA proteins from all influenza A H3N2 viruses. However, the functions of these two cysteines have not been fully studied. Here, we generated three mutants (C540S, C544L, and 2C/SL) to investigate the effects of the two TM cysteines on the biological functions of H3 HA. We herein presented evidences that the mutations of one or two of the cysteines did not affect the proper expressions of HA proteins in cells, and more importantly all mutant H3 HAs showed decreased thermal stability but increased fusion activity in comparison with wildtype HA. Our results taken together demonstrated that the two TM cysteines are important for the biological functions of H3 HA proteins.

[Research progress and prospect of universal influenza vaccine].

The constant outbreaks of influenza in a global scale have aroused great concern all over the world. Vaccine has been the most effective and economic means against influenza. However, the broad tropism and high mutation of influenza viruses have limited the effectiveness of influenza vaccines. Current influenza virus vaccines provide effective protection against virus strains that are identical or highly similar to the vaccine strain. Once a highly mutated or new strain of influenza virus appears, the current vaccine would lose its effectiveness. Therefore, the development of a universal vaccine against highly mutated or new influenza virus subtypes has become a hot spot in the field of influenza vaccine research. The major methods of developing the universal influenza vaccine are to select a conserved protein of influenza virus as an antigen. At least three universal influenza vaccines have been tested in clinical trials. Moreover, changing the routes of vaccine immunization and immunization schemes could also improve the effect of heterosubtypic immunity. This review summarized the research progresses of universal influenza vaccines and provided our prospective on universal influenza vaccine research.