Influenza virus M1 protein blocks the classical complement pathway
The genome of the influenza A virus is composed of eight segments of single stranded RNA, which exist as vRNP with nucleocapsid protein (NP) and RNA dependent RNA polymerase. vRNP is surrounded by matrix protein 1 (M1), which is the most abundant protein in influenza virus particles. It is widely accepted that M1 plays significant roles in many aspects of virus life cycle. M1 interacts with RNA and ribonucleoproteins, virus envelope protein, and is involved in transcription inhibition, RNP nuclear import/export, and budding process. M1 expressed on the infected cell surface is responsible for cross reactive recognition by cytotoxic T lymphocytes. Studies suggest that some M1 mutations affect virus particle morphology and are involved in virus-host protein interaction. Several host proteins have been found to associate with M1. These interactions implicate a broad range of biological significances, such as vRNP export and viral morphogenesis. The interactions between M1 and host proteins are critical for viral propagation but it is unknown if M1 protein has any effects on host immune responses.
This paper demonstrates that M1 protein is able to interact with complement C1qA and plays an important inhibitory function in the classical complement pathway. The N terminal domain of M1 protein is required for its binding to the globular region of C1qA. As a consequence, M1 blocks the interaction between C1qA and heat aggregated IgG in vitro and inhibits hemolysis. M1 protein prevents the complement mediated neutralization of influenza virus in vitro. In addition, studies on mice indicate that the administration of M1 can promote a higher virus propagation rate in lung and shortened survival of mice infected with the virus. Taken together, these results strongly suggest that M1 protein plays a critical role in protecting the influenza virus from host innate immune system.
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Tags: Biology, complement, Immunology, Influenza, Medicine, Microbiology, Science, Virology, virus
