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21 agosto 2015 5 21 /08 /agosto /2015 17:42

The sequence of antiviral genes suggests that African primates have been infected with lentivirus from 16 million years ago.

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Modelo del hexámero capsular de retrovirus, que muestra los dominios conservados (que varìan poco) beta-hairpin (círculo), estructura secundaria fundamental para la replicación y el procesamiento del viroide, comunes a la mayoría de tipos de retrovirus y muestra tambièn un bolsillo que contiene sitios adicionales que se cree que afecta el reconocimiento de los lentivirus por las proteínas de defensa TRIM5 anti-virales de monos del viejo mundo (flecha).

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Un estudio publicado en la revista PLOS Pathogens, presenta el reporte de científicos del Boston College (EEUU) que han investigado la historia de las adaptaciones que realizan tanto los virus como sus huéspedes, y sugieren que, en concreto, los lentivirus relacionados con el VIH han infectado a los simios africanos desde hace 16 millones de años.

Welkin Johnson, líder de la investigación, estudió un gen antiviral –que tienen en su genoma algunos primates– que codifica para una proteína llamada TRIM5.

“El gen de TRIM5 forma parte de los llamados "factores de restricción", factores que han evolucionado para proteger a las células del huésped de la infección de un virus”, remarca Welkin Johnson. Según el estudio, esta proteína, una vez que el lentivirus ha entrado en las células del huésped, interactúa con su membrana impidiendo que se multiplique.

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Dada su especificidad para los retrovirus, los investigadores plantearon que la evolución del gen de la proteìna de defensa TRIM5 en los monos africanos revelaría el tiempo que los lentivirus, muy vinculados a los SIV actuales, llevan infectándolos.

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Para esbozar un árbol filogenético de TRIM5, analizaron y compararon las secuencias de ADN de genes que codifican proteínas de 22 especies de primates africanos. Los cientìficos identificaron un grupo de cambios adaptativos únicos de las proteínas TRIM5 en solo un subconjunto de monos, los cercopitécidos.

Las variaciones en esta familia de primates, entre los que se incluyen macacos y babuinos, sugieren que los lentivirus ancestrales comenzaron su colonización en África hace entre 11 y 16 millones de años.

“La correlación entre las adaptaciones específicas para un linaje del virus y la capacidad de restringir los virus endémicos del anfitrión apoyan la hipótesis de que los ancestros de los SIV modernos llevan en África desde hace 16 millones de años”, concluye Johnson.

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Fig 4.  An evolutionarily-guided model for TRIM5α binding to capsid hexamers.

 

Fig 4. An evolutionarily-guided model for TRIM5α binding to capsid hexamers.

A. A capsid hexamer colored according to the key to highlight the sites identified in this study that modulate sensitivity to both Papionini and Cercopithecini TRIM5αs and their relation to sites that mediate contacts with cellular cofactors. A dashed circle shows the position of the β-hairpins. Black arrows point to a cluster of sensitizing mutations that sit between sites that mediate contacts with cyclophilin A/Nup-358-cypA-like domain, and those that mediate contacts with CPSF6/Nup-153. B. A model of TRIM5α (shades of orange) placed on the capsid hexamer. The V1 loops are colored yellow and indicated by yellow arrows. C and D are side views of A and B respectively. This model is based on a TRIM5 model published in Goldstone et al., 2014 [92] and provided by Ian Taylor.

 

doi:10.1371/journal.ppat.1005085.g004

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Tripartite motif-containing protein 5 also known as RING finger protein 88 is a protein that in humans is encoded by the TRIM5 gene. The alpha isoform of this protein, TRIM5α, is a retrovirus restriction factor, which mediates species-specific, early block to retrovirus infection.

TRIM5α is composed of 493 amino acids that is found in the cells of most primates. TRIM5α is an intrinsic immune factor important in the innate immune defense against retroviruses, along with the APOBEC family of proteins, tetherin and TRIM22.

TRIM5α belongs to the TRIM protein family (TRIM stands for TRIpartite Motif); this family was first identified by Reddy in 1992 as the proteins that contain a RING finger zinc binding domain, a B-box zinc binding domain, followed by a coiled-coil region. TRIM5α bears the C-terminal PRY-SPRY or B30.2 domain in addition to the other domains.

https://en.wikipedia.org/wiki/TRIM5alpha

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This is a model of a retrovirus capsid hexamer, showing the conserved beta-hairpin domains common to most kinds of retroviruses (circled) and a pocket containing additional sites thought to affect recognition of lentiviruses by the TRIM5 anti-viral defense proteins of old world monkeys (arrow). Credit: Johnson et al, CC-BY



Primates have been infected with viruses related to HIV for 16 million years


Disease-causing viruses engage their hosts in ongoing arms races: positive selection for antiviral genes increases host fitness and survival, and viruses in turn select for mutations that counteract the antiviral host factors. Studying such adaptive mutations can provide insights into the distant history of host-virus interactions. A new study of antiviral gene sequences in African monkeys suggests that lentiviruses closely related to HIV have infected primates in Africa as far back as 16 million years.

August 20, 2015 Source: PLOS

Disease-causing viruses engage their hosts in ongoing arms races: positive selection for antiviral genes increases host fitness and survival, and viruses in turn select for mutations that counteract the antiviral host factors. Studying such adaptive mutations can provide insights into the distant history of host-virus interactions. A study published on August 20th in PLOS Pathogens of antiviral gene sequences in African monkeys suggests that lentiviruses closely related to HIV have infected primates in Africa as far back as 16 million years.

Interested in the history of lentiviruses--the group of retroviruses to which HIV and its simian (monkey) relatives, the SIVs belong--Welkin Johnson, from Boston College, USA, and colleagues focused on an antiviral gene called TRIM5. TRIM5 is part of a group of antiviral genes called "restriction factors," which have evolved to protect host cells from infection by viruses. Its product, the TRIM5 protein, interacts directly with the outer shell of lentivirus particles after they enter the host cells and prevents the virus from multiplying there. (The human version of TRIM5 does not interfere with--and therefore not protect against--HIV, but many monkeys have TRIM5 variants that do render HIV harmless and are therefore immune to HIV/AIDS.)


Because of its unique specificity for retroviruses (whereas other restriction factors often have broader antiviral activity), the researchers hypothesized that the evolution of TRIM5 in African monkeys should reveal selection by lentiviruses closely related to modern SIVs. To derive an evolutionary tree of the TRIM5 gene, they analyzed and compared its complete protein-coding DNA sequences from 22 African primate species. They identified a cluster of adaptive changes unique to the TRIM5 proteins of a subset of African monkeys--the Cercopithecinae, which include macaques, mangabeys, and baboons--that suggests that ancestral lentiviruses closely related to modern SIVs began colonizing primates in Africa as far back as 11-16 million years ago.

The scientists also generated a panel of (reconstructed) ancestral and existing TRIM5 genes (19 total), expressed them in cultured cell lines, and exposed the cells to 16 different retroviruses (lentiviruses and others) to see which TRIM5 versions conferred resistance to which viruses. These experiments confirmed that the observed cluster of adaptations resulted in resistance specifically to cercopithecine lentiviruses, but had no effect on restriction of other retroviruses, including lentiviruses of other, non-cercopithecine primates.

The researchers conclude "The correlation between lineage specific adaptations and ability to restrict viruses endemic to the same hosts supports the hypothesis that lentiviruses closely related to modern SIVs were present in Africa and infecting the ancestors of cercopithecine primates as far back as 16 million years ago, and provides insight into the evolution of TRIM5 specificity."
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Evolutionary and Functional Analysis of Old World Primate TRIM5 Reveals the Ancient Emergence of Primate Lentiviruses and Convergent Evolution Targeting a Conserved Capsid Interface”. PLOS Pathogens.  20 de agosto de 2015.

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Evolutionary and Functional Analysis of Old World Primate ...

journals.plos.org/plospathogens/article?id=10...
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hace 21 horas - The widespread distribution of lentiviruses among African primates, and the lack of ... We analyzed complete TRIM5 coding sequences of 22 Old World ... ofOld World Primate TRIM5 Reveals the Ancient Emergence of Primate Lentiviruses and Convergent Evolution Targeting a Conserved Capsid Interface.

 

 

 

Primates have been infected with viruses related to HIV for ...

www.sciencedaily.com/releases/.../150820144714.ht...

 

Primates have been infected with ancestors of viruses such ...

www.ibtimes.co.uk/primates-have-been-infected-anc...

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https://en.wikipedia.org/wiki/TRIM5alpha

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Virus: estudio molecular con orientación clínica

https://books.google.com.pe/books?isbn=9500618796
Teri Shors - 2009 - ‎Medical
Una estructura secundaria, las protuberancias del dominio C conservado, son fundamentales para la replicación y el procesamiento del viroide. El dominio P se .

 

 

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