How Influenza A virus evades immune responses and its effects on the immune system responses

Running Title: Influenza A virus: Evasion and immune responses The purpose of this paper was to analyze and get a better understanding of how Influenza A virus (IAV), better known as the common flu, bypasses the highly sophisticated immune system. An example on how the innate and adaptive immune system reacts to IAV such as the H1N1 virus will also be discussed. Influenza A is the cause for the seasonal flu and pandemics such as the one in 2009 [1]. The main cause of IAVs ability to evade the immune system is due to antigenic drift, which is able to bypass immune recognition. The six steps required for entry and replication of IAV will also be analyzed in detail.

The influenza (flu) virus can be categorized into two main types, Type A and B. These are the two main types that cause the seasonal flu epidemics each year [2]. Influenza A can be broken down into subtypes, this is determined by the genes that makeup the surface proteins. The H1N1, H1N2, H3N2 and H2N2 are all subtypes of influenza A. Influenza A strains can affect the immune system because those strains are constantly changing overtime. How influenza escapes the immune system and the effects of immune system responses will be discussed throughout this paper. In a Review article by John Nicholls, he explains the battle between influenza and the innate immune system in the Human respiratory tract. The interaction of influenza with the innate immune defense system mechanism occurs in two phases. The first one is to escape from natural extracellular host barriers, and the second is hijacking the intracellular pathways by the virus to prevent an antiviral response from the immune system and replicate [3]. Mucin, host defense lectins and alveolar macrophages are the three barriers that influenza needs to pass in order for infection to occur. The influenza virus is able to surpass the host defense mechanism due to the surface protein haemaglutinin (HA) and neuraminidase (NA). The first barrier that influenza needs to pass is mucin. Mucin is what holds mucus together. Mucus is a mixture of cells, cellular debris and polypeptides. Mucins are able to trap influenza viruses, but the ability of influenza to infect the respiratory epithelium is due to the prefer­ence of the viral NA to cleave α2-3 linkages compared with α 2-6 linkages [3]. The second barrier that the influenza virus needs to overcome is host defense lectins. Influenza is able to overcome these lectins by lacking glycosylation of HA compared to viruses that have been glycosylated. The third barrier that influenza needs to avoid is macrophages; alveolar macrophages are equally susceptible to human and avian influenza virus infection [3]. Influenza is able to hijack the innate immune system and develop the ability to evade the IFN defense mechanism. Garcia-Sastre was able to prove that influenza lacks a gene called non-structural protein (NSI) and is able to suppress the IFN pathway [3]. The IFN pathway is suppressed due to the fact that NS1 targets TRIM25, which is the initiator for the activation of RIG-I. RIG-I causes the production of IFN. TRIM25 interacts with all influenza strains, NS1 can also prevent PKR from being produced, thus allowing virus propagation to keep on [4]. Edinger and colleagues have recently analyzed the entry of influenza A virus, and have determined that there are six steps to complete replication. The six steps are attachment to target cells, internalization into cellular compartments, endosomal trafficking to the perinuclear region, fusion of viral and endosomal membranes, uncoating, and import of the viral genome into the nucleus [5]. Each step will be analyzed even further to understand how influenza A strains are so successful. Attachment of host cells is the first step of influenza