Human virome

The human virome is the collection of all the viruses in the human body.[1][2][3] Viruses are the most abundant infectious agents on the planet.[4] These include viruses that cause acute self-limiting or uncontrolled infections, persistent and chronic infections that may or may not be asymptomatic, or latent infections, they also include viruses that are integrated in the human genome.[1] Humans are constantly exposed to a variety of viruses that are genetically diverse and have new genotypes, strains and species that evolve rapidly.[5] Every human being has a unique virome with a unique balance of species that can change quickly.[2][6] Lifestyle, age, geographic location, and even the season of the year affects an individual's exposure to viruses; while their susceptibility to disease is effected by preexisting immunity and both viral and human genetics.[7] The first virus that was discovered was the Tobacco mosaic virus in 1892 and viruses are still being discovered today.[5] With today's technological advances, more viruses are rapidly being discovered in the environment and within the human body.

Health effects

The human virome is a part of our bodies and will not always cause harm. Many latent and asymptomatic viruses are present in the human body all the time. Viruses infect all life forms; therefore the bacterial, plant, and animal cells and material in our gut also carry viruses.[6] Through one's immune system, the body has the ability to protect itself from other viruses that may cause disease. When viruses cause harm by infecting the cells in the body, a symptomatic disease may develop. Contrary to common belief, harmful viruses may be in the minority compared to benign viruses in the human body. It is much harder to identify viruses than it is to identify bacteria, therefore our understanding of benign viruses in the human body is very rudimentary.[2]

The health effects of viruses on an individual are dependent on the individual's immune function and cell surface proteins, which are determined by genetics and vary with genetic polymorphisms across the population and over time in relation to age and other factor determining immune status.[1][8]

The hygiene hypothesis

Recent research has linked the emerging idea of the hygiene hypothesis to viruses. This hypothesis attempts to explain and justify some of the high incidences of diseases such as asthma[9] and eczema[10] in the Western world to Western society's overuse of antibiotic and antiviral agents. This overuse potentially disrupts not only the bacteria of the gut but also the viruses that have long lived in harmony with the human body and now play a role in regulation of human health. This hypothesis generally refers to microorganisms but is now being extended to include airborne viruses and common viral infections of childhood that are becoming increasingly less common.[11]

Effect of diet

Many studies have demonstrated that the bacteria and viruses in the human gut (the gut microbiome) can be altered by changes in diet. One study that focused on bacterial viruses, called bacteriophages, in the gut found a significant relationship between diet and the type of bacteriophages present.[12] This was done by comparing the distance between bacteriophage gut communities in individuals both before and after they started a controlled diet. The results were that the distance between the bacteriophage gut communities of individuals on the same diet was significantly smaller at the end of their dietary treatment than it was at the start, while there was no increase in community similarity for individuals on different diets over time.

Research

The human microbiome project funded by the National Institute of Health aims to characterize all of the microbes, including viruses, present in various body sites including nasal passages, oral cavities, skin, gastrointestinal tract, and urogenital tract.[13] Defining the virome will help understand microbes and how they affect human health and disease.[1] A study of currently recognized species is a starting point for attempts to characterize and interpret patterns of virus diversity.[5] Samples can be collected from human serum, plasma, saliva, gastrointestinal tract, urine, skin swabs and more.[4][7][14][15][16] Samples from children and immunocompromised patients would yield the most exposure to new viruses because the viral loads are expected to be higher in these individuals.[7] Although several projects have been proposed, no study has yet characterized the virome of human pathogens in a comprehensive and systematic way.[8]

The objective of analyzing the human virome is to monitor which agents change over time, find undiscovered agents already present, and detect new viruses when they appear.[7][14][15] It is important to study viruses because they are critical determinants of bacterial community structure and function in all habitats.[4][8] Viruses disperse quickly, meaning a global surveillance network is essential to ensure rapid detection. A better understanding of the emergence of new human viruses as a biological and ecological process will allow refinement of the current notion of the kinds of pathogens, or the kinds of circumstances, that are of most concern, and so direct efforts at detection and prevention.[5] As the depth of sequencing expands and the database of viral genomes becomes larger, the easier diagnosis of previously unidentified viral-associated conditions will become.[17] Future investigations of host-virome interactions hold great promise for providing new approaches to combating complex diseases.[8] Lastly, studying the virome could help improve drug development and limit antibiotic usage.[2][15][16]

Research methods and tools

Multiple methods are available for the classification and isolation of all classes of viruses.

Deep sequencing

Deep sequencing is a rapid DNA sequencing technique that is useful for characterizing virome richness, stability, gene function and the association with disease phenotypes.[1][3] This technology creates large amounts of sequence information and is capable of detecting rare components of a microbial community.

Current methods combining the removal of human and bacterial DNA from samples, large scale sequencing, and bioinformatics are very efficient in the identification of unknown viruses. Unlike other discovery methods, viruses do not need to be grown in cell cultures. Without any prior knowledge of genome sequence or growth methods, novel viruses can be discovered. Therefore deep sequencing is well suited for rapid identification of an unknown or unexpected viruses involved in a disease outbreak or associated with conditions not thought to be caused by viruses. Deep sequencing also allows for large scale screenings with minimal hands on effort.[18] A systematic exploration of the viruses that infect humans (the human virome) is important and feasible with these methods.

Polymerase chain reaction

The Polymerase chain reaction is a tool to amplify and detect specific DNA sequences. It can be used to help characterize the virome, but it is limited by the need for at least partial DNA sequence information.

The Human Metagenome

The Human Metagenome includes all organisms that live on or in us. Viruses contribute to the metagenome and establish chronic infection that infest chromosomes; this method will formulate new estimate of the number of genes that confer susceptibility to a given virus and specify alleles for some viruses.[19][20]

ELISA

Large scale antibody studies with ELISA using donated blood could help to determine human exposure to particular viruses in different geographic regions.[7]

References

  1. 1 2 3 4 5 Wylie, Kristine M.; Weinstock, George M.; Storch, Gregory A. (1 October 2012). "Emerging view of the human virome". Translational Research 160 (4): 283–290. doi:10.1016/j.trsl.2012.03.006.
  2. 1 2 3 4 Williams, S. C. P. (6 February 2013). "The other microbiome". Proceedings of the National Academy of Sciences 110 (8): 2682–2684. doi:10.1073/pnas.1300923110.
  3. 1 2 Fontana, Judith M.; Alexander, Elizabeth; Salvatore, Mirella. "Translational research in infectious disease: current paradigms and challenges ahead". Translational Research 159 (6): 430–453. doi:10.1016/j.trsl.2011.12.009.
  4. 1 2 3 Pride, David T; Salzman, Julia; Haynes, Matthew; Rohwer, Forest; Davis-Long, Clara; White, Richard A; Loomer, Peter; Armitage, Gary C; Relman, David A (8 December 2011). "Evidence of a robust resident bacteriophage population revealed through analysis of the human salivary virome". The ISME Journal 6 (5): 915–926. doi:10.1038/ismej.2011.169.
  5. 1 2 3 4 Woolhouse, M.; Scott, F.; Hudson, Z.; Howey, R.; Chase-Topping, M. (10 September 2012). "Human viruses: discovery and emergence". Philosophical Transactions of the Royal Society B: Biological Sciences 367 (1604): 2864–2871. doi:10.1098/rstb.2011.0354.
  6. 1 2 Zimmer, Carl. "Your Inner Lions: Get to Know Your Virome". National Geographic. Retrieved 29 April 2013.
  7. 1 2 3 4 5 Delwart, Eric; Racaniello, Vincent (14 February 2013). "A Roadmap to the Human Virome". PLoS Pathogens 9 (2): e1003146. doi:10.1371/journal.ppat.1003146.
  8. 1 2 3 4 Foxman, Ellen F.; Iwasaki, Akiko (1 April 2011). "Genome–virome interactions: examining the role of common viral infections in complex disease". Nature Reviews Microbiology 9 (4): 254–264. doi:10.1038/nrmicro2541.
  9. ↑ Butler, Christopher C (September 2013). "Asthma prevalence and humoral immune response in Somali immigrants in the US: implications for the hygiene hypothesis.". Primary Care Respiratory Journal: Journal of the General Practice Airways Group 22 (3): 262–264. doi:10.4104/pcrj.2013.00081.
  10. ↑ Strachan, David P (June 10, 2014). "Siblings, Asthma, Rhinoconjunctivitis And Eczema: A Worldwide Perspective From The International Study Of Asthma And Allergies In Childhood.". Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology 45: 126–136. doi:10.1111/cea.12349.
  11. ↑ Daley, D (October 2014). "The evolution of the hygiene hypothesis: the role of early-life exposures to viruses and microbes and their relationship to asthma and allergic diseases.". Current opinion in allergy and clinical immunology 14 (5): 390–396. doi:10.1097/ACI.0000000000000101.
  12. ↑ Minot, S.; Sinha, R.; Chen, J.; Li, H.; Keilbaugh, S. A.; Wu, G. D.; Lewis, J. D.; Bushman, F. D. (31 August 2011). "The human gut virome: Inter-individual variation and dynamic response to diet". Genome Research 21 (10): 1616–1625. doi:10.1101/gr.122705.111.
  13. ↑ "Human Microbiome Project". National Institutes of Health. Retrieved 30 May 2013.
  14. 1 2 Anderson, Norman G.; Gerin, John L.; Anderson, N. Leigh (1 July 2003). "Global Screening for Human Viral Pathogens". Emerging Infectious Diseases 9 (7): 768–773. doi:10.3201/eid0907.030004.
  15. 1 2 3 Dalke, Kate. "The Human Virome". Genome News Network. Retrieved 2 April 2013.
  16. 1 2 Pennisi, E. (24 March 2011). "Going Viral: Exploring the Role Of Viruses in Our Bodies". Science 331 (6024): 1513–1513. doi:10.1126/science.331.6024.1513. PMID 21436418.
  17. ↑ Handley, SA; Thackray, LB; Zhao, G; Presti, R; Miller, AD; Droit, L; Abbink, P; Maxfield, LF; Kambal, A; Duan, E; Stanley, K; Kramer, J; Macri, SC; Permar, SR; Schmitz, JE; Mansfield, K; Brenchley, JM; Veazey, RS; Stappenbeck, TS; Wang, D; Barouch, DH; Virgin, HW (Oct 12, 2012). "Pathogenic simian immunodeficiency virus infection is associated with expansion of the enteric virome.". Cell 151 (2): 253–66. doi:10.1016/j.cell.2012.09.024. PMID 23063120. Cite uses deprecated parameter |coauthors= (help)
  18. ↑ Allander, T. (6 September 2005). "From The Cover: Cloning of a human parvovirus by molecular screening of respiratory tract samples". Proceedings of the National Academy of Sciences 102 (36): 12891–12896. doi:10.1073/pnas.0504666102. PMC 1200281. PMID 16118271.
  19. ↑ Virgin, Herbert W.; Wherry, E. John; Ahmed, Rafi (1 July 2009). "Redefining Chronic Viral Infection". Cell 138 (1): 30–50. doi:10.1016/j.cell.2009.06.036.
  20. ↑ Kristensen, David M.; Mushegian, Arcady R.; Dolja, Valerian V.; Koonin, Eugene V. "New dimensions of the virus world discovered through metagenomics". Trends in Microbiology 18 (1): 11–19. doi:10.1016/j.tim.2009.11.003. PMC 3293453. PMID 19942437.
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