Viral and Host Protein Interactions

Viruses are undoubtedly a constant nightmare in the medical world, and their active capacity to mutate and adapt to new conditions turns them into complex enemies for our immune systems. Elucidating how each virus strain infects human cells has always been one of the most useful tools in the development of more efficient vaccines and antivirals.

Introduction to Viruses

A virus can attack all types of life forms, but they can only replicate inside the living cells of the organism they infect. Furthermore, all viruses present variations in their genomic composition and these, along with other differences, are crucial to the way they infect (1).

A virus that is not inside an infected cell is known as virion and can be found in almost every ecosystem. It consists of genetic material that may be DNA or RNA and a protein capsid that surrounds and protects the genome. In some virions the capsid is surrounded by an external envelope of lipids (1). Due to their lack of certain cell characteristics (cell membrane, nucleus, organelles) and their need of a host to concrete their replication, viruses are classified by scientists as “‘organisms at the edge of life (2).”

Viruses can spread in many different ways: passed from host to host by contact, carried by vectors such as insects that behave as agents of transmission, and through sexual contact, among other paths (3). Some viruses are specific to one host, while others can infect a wide range of species. Depending on the degree of virulence and the targeted cells, a virus can be harmless or it can cause complex diseases such as cancer, hepatitis C, or AIDS (3).

Viral infection triggers an immune response in the host that usually eliminates the agent; however, many viruses evade the mechanisms of defense and cause chronic infections. Antivirals and vaccines are produced to combat infection. Antibiotics are innocuous against viruses but sometimes useful in cases of coinfection of a virus and bacteria. Due to the high mutation rate of some virus strains, many vaccines are only seasonally effective and require new vaccines to be released every year in order to fight against the new mutant (4). For instance, this is the case for the vaccine against influenza.

Virus Interactions with the Host

The specific binding between a virus and the host cellular surface is known as “attachment” and is mediated by the proteins that conform the capsid and the protein receptors in the cell membrane (5). Protein-protein interactions (PPIs) are the key mediators of the host-pathogen relationship (6). Specificity of some viruses to some cells relies on these interactions (6). To study virus-host protein interactions, laboratories use modern technology and equipment that extend knowledge about viral and host protein architectures. This biological data provides insights into the molecular mechanisms of pathogenicity that are essential to the understanding of the life cycle of a pathogen in order to develop adequate therapeutic strategies.

In addition, pathogens have developed intricate tools to elude host defense mechanisms. It has been revealed that pathogens constantly rewire host cell defenses and that the phenotypic impact of a virus is directly related to its capacity to rewire the host interactome (7). This proposes that the impacts of virulent proteins are linked to their number of interactions with host proteins. Blocking such interactions is the main mechanism underlying antiviral therapies (8).

Science has proven that it is still relatively difficult to fight viruses with medication, so the development and research for new strategies that inhibit PPIs is an important step in the right direction to fighting nasty viral infections.

SOURCES:

  1. Koonin E, Senkevich T, Dolja V. The ancient Virus World and evolution of cells. Biol Direct. 2006; 1: 29. Published online 2006 Sep 19. doi:  10.1186/1745-6150-1-29
  2. Koonin E, Starokadomskyy P. Are viruses alive? The replicator paradigm sheds decisive light on an old but misguided question. Stud Hist Philos Biol Biomed Sci. Author manuscript; available in PMC 2017 Oct 1.b Published in final edited form as: Stud Hist Philos Biol Biomed Sci. 2016 Oct; 59: 125–134. Published online 2016 Mar 7. doi:  10.1016/j.shpsc.2016.02.016
  3. Lodish H, Berk A, Zipursky SL, et al. Molecular Cell Biology. 4th edition. New York: W. H. Freeman; 2000.
  4. Berzofsky J. Progress on new vaccine strategies against chronic viral infections. J Clin Invest. 2004 Aug 16; 114(4): 450–462. doi:  10.1172/JCI200422674
  5. Puck TT, Garen A, Cline J. The mechanism of virus attachment to host cells. I. The role of ions in the primary reaction. J Exp Med. 1951 Jan;93(1):65-88.
  6. Halehalli R, Nagarajaram H. Molecular principles of human virus protein-protein interactions. Bioinformatics. 2015 Apr 1;31(7):1025-33. doi: 10.1093/bioinformatics/btu763. Epub 2014 Nov 21.
  7. Nicod C, Banael A, Collins B. Elucidation of host-pathogen protein-protein interactions to uncover mechanisms of host cell rewiring. Curr Opin Microbiol. 2017 Oct;39:7-15. doi: 10.1016/j.mib.2017.07.005. Epub 2017 Aug 11.
  8. Brito A, Pinney J. Protein-Protein Interactions in Virus-Host Systems. Front Microbiol. 2017 Aug 17;8:1557. doi: 10.3389/fmicb.2017.01557. eCollection 2017.

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