Since Dutch researchers discovered human metapneumovirus (hMPV) in 2001, hMPV and its subtypes have been detected in many countries. hMPV is a respiratory pathogenic virus, which belongs to paramyxovirus, and can express a variety of proteins. Among them, the G, F, and M2 gene proteins are the focus of vaccine development, and people have a certain understanding of it. Currently known hMPV has two genotypes A and B and four subtypes A1, A2, B1, and B2. All subtypes can cause respiratory tract infections. There are many reports showing that severe or fatal diseases can occur after hMPV infection. Therefore, its immunity and related vaccines have been studied.
Main Structure and Expression Protein Analysis of hMPV
Under the electron microscope, hMPV showed a shape similar to paramyxovirus particles, and the particles were multi-shaped, spherical, and fibrous. The average particle diameter is 15nm, the nucleoprotein diameter is 17nm, and the nucleoprotein length is 200-1000nm. It has a non-segmental negative-helical single-stranded RNA structure with a shell membrane and belongs to the paramyxovirus family. hMPV is a single negative-strand non-phase RNA virus, the genome RNA length is about 13000 nucleotides, including 9 protein genes, the sequence is 3-N-P-M-F-M2-SH-G-L-5. Among all hMPV proteins, N protein often induces the body’s cellular immune response and mainly plays a role in virus clearance, while the antibodies it induces often lack neutralizing antibody activity; G and F glycoproteins are the main functional molecules for the virus to adhere to and infect target cells. It can induce the body to produce neutralizing antibodies, and is the most effective molecule found so far to protect the body from infection.
G Protein-mediated Cellular Immune Response
As a membrane protein component, G protein has frequent contact with the body’s immune system and plays an important role in the pathogenic mechanism. G protein can induce the body to produce neutralizing antibodies, which is the most important way for the body to prevent infection. By observing the response of bronchoalveolar lavage (BAL) cells to inflammation, it was found that the expression of RSV G protein was closely related to the expression of Th1 cytokines, chemokines CC and CXC. Because the G protein of RSV and the G protein of hMPV have similar structures, the G protein of hMPV may be closely related to Th1 cell immunity and the expression of related inflammatory factors. By using the BALB/c mouse model, it was found that hMPV infection is not only related to the weakening of innate immune response and the inert immune response mediated by CD4 T cells in the lung, but also to the decreased expression of interferon in the later stage of infection, and local interferon plays a role in restricting the virus. Plays a vital role in replication and body defense. After hMPV infection, the body’s immune response can be triggered by the expression of Th1 or Th2 cytokines. There is an interactive negative feedback regulation between Th1 and Th2 immune responses: interferon produced by Th1 can promote Th1-type responses and inhibit Th2-type responses; while interleukin-10 produced by Th2 has the opposite effect. The results of cell counting analysis showed that in the early stage of hMPV infection, the levels of Th1-type cytokines interleukin-2, interferon-γ, and tumor necrosis factor-α produced by CD4 T cells were higher; in the later stage of hMPV infection, the level of Th2 cytokine interleukin 10 produced by CD8 T cells was higher. The study also found that when the level of interferon gamma produced by CD8 T cells is low and the level of interleukin 10 produced by CD4 T cells and CD8 T cells is high, the corresponding level of viral replication in the lungs will also be at a high level, indicating that cytokines The regulation of secretion and the amount of expression are closely related to the occurrence of virus replication and infection. Viruses can also adopt various methods, including replication of immune privileged sites, downregulation of immune molecules, antigen mutation, and molecular mimicry to weaken the body’s immune response. Further infection of the nasopharynx of BALB/c mice with hMPV was found to cause clinical symptoms such as lung inflammation, airway obstruction, and airway hyperresponsiveness in mice, and CD4+ and CD8+ T cells were able to synergistically clear the hMPV, but more CD4+ T cells also aggravated clinical symptoms and lung pathological changes. Although the body’s ability to neutralize antiviral antibodies was weakened after CD4+T cell deletion, the pathological changes and clinical symptoms of the lungs were alleviated, indicating that intact CD8+T cells provided immune protection for the body.
G protein Can Suppress the Body’s Innate Immune Response
The latest research shows that the G protein plays an important role in the replication of the virus both in vivo and in vitro. The recombinant hMPV (rhMPVΔDG) with the G protein removed was used to infect the respiratory tract of Syrian hamsters and African green monkeys. In contrast, the MPV replication ability in Syrian hamsters and African green monkeys was significantly weakened. Since the G protein can inhibit the pro-inflammatory response and the secretion of antiviral molecules, the replication ability and pathogenic effect of rhMPVΔDG are weakened, which is also similar to the G protein of RSV. In addition, the G protein in rhMPV can also inhibit the innate immune response of the infected host and play an important role in regulating signal transduction pathways. It can affect nuclear factor κB, interferon regulatory factors, cytokines, chemokines and other genes Regulate the production of proinflammatory response molecules and the secretion of interferon through the expression of pro-inflammatory response molecules; weaken the host beta interferon, interleukin 8 and chemokine RANTES (regulate the activation of normal T Cell-expressed and secreted chemokines) gene transcription, thereby increasing the ability of virus replication. And it can also inhibit the inflammatory response of interferon-alpha and interferon-beta by blocking signal transduction and phosphorylation of transcriptional kinase factors, eventually leading to respiratory tract infection and pathogenicity. In conclusion, G protein plays an extremely important role in the rhMPV infection process.
Vaccine Research
Now it has been confirmed that hMPV is an important pathogen causing acute respiratory infection in infants and children with low immunity. The infection rate is 4% to 15%, second only to RSV infection, and its incidence rate is even reported as high as 25.3%. Currently there is no effective way to avoid hMPV infection, so research on hMPV vaccines is also ongoing. The research on virus vaccines began in the 1860s at the earliest. After the formaldehyde-inactivated RSV vaccinators were infected by RSV again, the infection appeared to be significantly aggravated. Since this phenomenon could not be explained at that time, the virus vaccine was abandoned. Further research, and later animal experiments proved that this phenomenon is caused by the imbalance of Th2’s response to viral antigens. Because the hMPV membrane surface glycoprotein has important homology with RSV, it also hinders the research and development of hMPV vaccine; however, there have been many reports about virus vaccines in recent years, and the current vaccine trials are mainly in the G of hMPV. Protein, F protein and M2-2 protein research basis.
