Humanos would not have existed without virus because viral protein plays a key role in the development of humana embryo. However, at times, they pose existential threats in the form of diseases as in the case of current COVID-19 pandemic. Ironically, virus comprise ~8% of our genome, that has been acquired during the course of evolution, making us “virtually a chimera”.
La palabra más infame y espantosa del año 2020 sin duda es 'virus'. La novela coronavirus es responsable de la actual enfermedad COVID-19 sin precedentes y de un casi colapso de la economía mundial. Todo esto es causado por una pequeña partícula que ni siquiera se considera "plenamente" viva porque se encuentra en un estado no funcional fuera del anfitrión, mientras que solo se perpetúa en el interior al infectar al anfitrión. Más sorprendente e impactante es el hecho de que los seres humanos. have been carrying the viral “genes” since times immemorial and currently viral genes constitutes ~8% of the humana genome (1). Just to put this in perspective, only ~1% humana genome is functionally active responsible for making proteins that determine who we are.
The story of relationship between los seres humanos. y virus started 20-100 million years ago when our ancestors got infected by virus. Each endogenous retrovirus family is derived from a single infection of the germline cells by an exogenous retrovirus that after integrating into our ancestor, expanded and evolved (2). The propagation followed by the horizontal transfer from parents to offspring and today we have these viral genomes embedded in our DNA as humana endogenous retroviruses (HERVs). This is a continuous process and may even be happening at the moment. Over the course of evolution, these HERVs acquired mutations, became stabilised in the humana genome and lost their ability to cause the disease. The endogenous retrovirus are not only present in los seres humanos. but are omnipresent in all living organisms. All these endogenous retroviruses grouped into three classes (Class I, II and III) occurring across different animal species exhibit a phylogenetic relationship based on their sequence similarity (3) as depicted in Figure below. HERVs belong to the Class I group.
Of the various embedded retroviruses present in the humana genome, a classic example worth mentioning here, is that of a retroviral protein that is highly fusogenic envelope protein called syncytin, (5) whose original function in the virus was to fuse with host cells to cause infection. This protein has now been adapted in los seres humanos. to form placenta (fusion of cells to make multinucleated cells) that not only provides food to foetus from the mother during pregnancy but also protects the foetus from the mother’s immune system due to the immunosuppressive nature of the syncytin protein. This particular HERV has proven to be beneficial to the humana race by defining its very existence.
HERVs have also been implicated in providing innate immunity to the host by preventing further infection from related virus or reducing the severity of the disease upon re-infection by similar type of virus. A 2016 review by Katzourakis and Aswad (6) describes that endogenous virus can act as regulatory elements for genes that control immune function, thereby leading to immunity development. In the same year, Chuong et al (7) demonstrated that certain HERVs act as regulatory enhancers by modulating the expression of IFN (interferon) inducible genes thereby providing innate immunity. HERV expression products can also act as pathogen-associated molecular patterns (PAMPs), triggering the cellular receptors responsible for host first line of defences (8-10).
Otro aspecto interesante de los HERV es que algunos de ellos muestran polimorfismos de inserción, es decir, hay un número diferente de copias presentes en el genoma debido a eventos de inserción. Un estudio de 20 sujetos pertenecientes a diferentes grupos étnicos reveló patrones de polimorfismo de inserción entre 0-87% en todos los sujetos (11). Esto puede tener implicaciones a la hora de causar enfermedades mediante la activación de ciertos genes que, de otro modo, serían silenciosos.
También se ha demostrado que ciertos HERV están asociados con el desarrollo de trastornos autoinmunes como la esclerosis múltiple (12). En condiciones fisiológicas normales, la expresión de HERV está estrictamente regulada, mientras que en condiciones patológicas debido a cambios en el entorno externo / interno, los cambios hormonales y / o la interacción microbiana pueden causar una desregulación de la expresión de HERV, lo que conduce a la enfermedad.
The above characteristics of HERVs suggest that not only their presence in humana genome is inevitable but they possess the ability to regulate the homeostasis of the immune system either by activating or suppressing it, thereby causing differential effects (from being beneficial to causing a disease) in hosts.
The COVID-19 pandemic is also caused by a retrovirus SARS-nCoV-2, that belongs to the influenza family, and it may be plausible that, during the course of evolution, genomes related to this family of virus got integrated into the humana genome and are now present as HERVs. It is surmised that these HERVs might exhibit different polymorphisms, as mentioned above, among people of different ethnicity. These polymorphisms may be in the form of differential copy number of these HERVs and/or presence or absence of mutations (changes in the genome sequence) accumulated over a period of time. This variability in the integrated HERVs may offer an explanation for the differential mortality rates and the severity of COVID-19 disease in different countries effected by the pandemic.
***
Referencias:
1. Griffiths DJ 2001. Endogenous retroviruses in the humana genome sequence. Genome Biol. (2001); 2(6) Reviews 1017. DOI: https://doi.org/10.1186/gb-2001-2-6-reviews1017
2. Boeke, JD; Stoye, JP (1997). "Retrotransposones, retrovirus endógenos y la evolución de retroelementos". En Coffin, JM; Hughes, SH; Varmus, HE (eds.). Retrovirus. Prensa de laboratorio de Cold Spring Harbor. PMID 21433351.
3. Vargiu L, et al. Classification and characterization of humana endogenous retroviruses; mosaic forms are common. Retrovirology (2016); 13: 7. DOI: 10.1186 / s12977-015-0232-y
4. Classes_of_ERVs.jpg: Jern P, Sperber GO, Blomberg J (trabajo derivado: Fgrammen (charla)), 2010. Disponible en línea en https://commons.wikimedia.org/wiki/File:Classes_of_ERVs.svg Consultado el 07 de mayo de 2020.
5. Blond, JL; Lavillette, D; Cheynet, V; Bouton, O; Oriol, G; Chapel-Fernandes, S; Mandrandes, S; Mallet, F; Cosset, FL (7 April 2000). “An envelope glycoprotein of the humana endógeno retrovirus HERV-W is expressed in the human placenta and fuses cells expressing the type D mammalian retrovirus receptor”. J. Virol. 74 (7): 3321–9. DOI: https://doi.org/10.1128/jvi.74.7.3321-3329.2000.
6. Katzourakis A, and Aswad A. Evolution: Endogenous Los virus Provide Shortcuts in Antiviral Immunity. Current Biology (2016). 26: R427-R429. http://dx.doi.org/10.1016/j.cub.2016.03.072
7. Chuong EB, Elde NC y Feschotte C. Evolución reguladora de la inmunidad innata a través de la cooptación de retrovirus endógenos. Ciencia (2016) Vol. 351, número 6277, págs. 1083-1087. DOI: https://doi.org/10.1126/science.aad5497
8. Wolff F, Leisch M, Greil R, Risch A, Pleyer L. La espada de doble filo de la (re) expresión de genes mediante agentes hipometilantes: desde la mimetización viral hasta la explotación como agentes de cebado para la modulación de puntos de control inmunitarios dirigidos. Señal de comunicación celular (2017) 15:13. DOI: https://doi.org/10.1186/s12964-017-0168-z
9. Hurst TP, Magiorkinis G. Activation of the innate immune response by endogenous retrovirus. J Gen Virol. (2015) 96:1207–1218. DOI: https://doi.org/10.1099/vir.0.000017
10. Chiappinelli KB, Strissel PL, Desrichard A, Chan TA, Baylin SB, Correspondence S. La inhibición de la metilación del ADN provoca una respuesta de interferón en el cáncer mediante dsRNA que incluye retrovirus endógenos. Cell (2015) 162: 974–986. DOI: https://doi.org/10.1016/j.cell.2015.07.011
11. Mehrab G, Sibel Y, Kaniye S, Sevgi M and Nermin G. Human endogenous retrovirus-H insertion screening. Molecular Medicine Reports (2013). DOI: https://doi.org/10.3892/mmr.2013.1295
12. Gröger V y Cynis H. Retrovirus endógenos humanos y su supuesta función en el desarrollo de trastornos autoinmunes como la esclerosis múltiple. Microbiol frontal. (2018); 9: 265. DOI: https://doi.org/10.3389/fmicb.2018.00265
***
