Viral Evasive Strategies: dodging the immune system

Charles Darwin described evolution by his famous statement “struggle for the existence”. Nature always like predator-prey play. Our body evolved a complex network of immune system to combat with different kind of external organism and substances like virus. Viruses also have a place in nature and also meant to survive. Therefore, they also developed different evasive strategies to dodge the immune system. Today we will know how virus avoid immune attack after entering into our body.

Virus have developed multiple strategies to counteract host immune system. Avoiding immune clearance is very essential for virus because it helps to persist within their host for extended time. For pathogenic virus, it even facilitates prolong infection, in addition, also provide enough time with better opportunities to spread out in new hosts. Some common evasive strategies are described here:

Immune defense is mainly based on interaction or binding ability of immune components with antigen (whole virus or a part of a virus i.e., surface glycoprotein). Viruses can change their surface glycoproteins (antigens) which make them unknown to antibodies, an immune component. Viral spike protein (trimeric viral hemagglutinin) and neuraminidase are two major antigens which provide such facilities. To change these proteins, viral genomes undergo mutations in genes encoding these surface proteins. Of course it is not preprogrammed rather random events of error prone nature of viral genomes. The mutations in viral DNA together with antigenic drift and reassortment of viral genome causes huge antigenic variation which is known as antigenic shift. For example, HIV is an expert in producing antigenic variation. Needless to say, this property of HIV makes us unable to develop vaccine against HIV. However, prophylactic vaccination against invariant viral proteins could be useful in these conditions.


Figure: Some viral evasive strategies to fight against host immunity

Some viruses inhibit or alter the way of antigen processing and presentation. These are the prerequisite for antibody-antigen interaction to occur. Major histocompatibility complex (MHC) process and present these antigens to antibody. Viruses make different kinds of proteins that block different steps in antigen processing, transport and presentation. Consequently, cell infected by such viruses cannot be identified of killed by CD8+ CTLs. However, natural killer cells (NK) may have evolved as an adaption to this supersmart evasive strategy. NK cells are activated by virus infected cells, especially when class I MHC molecules are compromised. Viruses are getting even smarter. There is evidence that some viruses already got their tickets in such condition too. They produce proteins that act as ligands for inhibitory receptors of NK cells, thus, inhibit NK cell activation.

Some viruses can even inhibit immune response and attack host almost silently. For instance, Poxviruses produce some molecules i.e., TNF, IFN-γ, IL-1, IL-18 and chemokines which secreted by the infected cells. These molecules bind to several specific cytokines and may act as competitive antagonists against cytokines. Epstein-Barr viruses encode a protein homologous to cytokine IL-10. Cytokine IL-10 inhibits the activation of dendritic cells and macrophages, thus, restricts cell mediated immunity. Also, some viruses can infect and either kill or inactivate immunocompetent cells. Again, the best example is HIV which survives by infecting and eliminating CD4+ T cells, the key promoter of immune responses to antigens.

Every time one is trying to be smarter than its counter organisms. This is how we end up here and still evolving. So, the battle between microbes and host organisms is probably a never ending process of nature. In fact, these are the proof of the constant evolutionary struggle between microbes and host immunity.


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