Endogenous Viral Etiology of Prion Diseases

Transmissible spongiform encephalopathies (TSEs), or prion diseases, are a group of incurable neurodegenerative disorders, including Kuru and Creutzfeldt-Jakob disease in humans, “mad cow” disease in cattle, and scrapie in sheep. This paper presents structural, genetic, and evolutionary evidence supporting an endogenous TSE virus model that integrates the three major traditional views on the nature of TSE pathogens, the conventional virus view, the prion hypothesis, and the virino concept, into a novel conceptual and evolutionary framework. According to this model, the TSE pathogens are symbiotic endogenous viruses that inadvertently produce transmissible viral particles that lack the viral genome and are composed primarily of the viral prion protein (PrP). Production of defective viral particles that contain a partial genome or lack the viral genome entirely is a relatively common event in the life cycle of many viruses. Similar to the normal viral particles, which contain a genome, these defective viral particles can be transmitted to new host cells. Obviously, in the absence of viral genome, these protein-only viral particles cannot establish a productive infection. However, if these viral particles enter a host cell that carries the parental or a related virus and induce the production of similar protein-only particles, then they would appear as self-replicating, protein-only infectious pathogens if mistakenly taken out from the context of the viral life cycle. This misconception, which is rooted into the current dogma of viruses as viral particles, led to the development of the prion theory. The endogenous TSE virus model is consistent with the TSE data and offers solutions to many enigmatic features associated with TSE, including the function of PrP that, despite more than two decades of TSE research conducted primarily within the framework of the prion hypothesis, is still not known. According to the TSE endogenous virus model, PrP is the protein of an endogenous virus that has co-evolved with their vertebrate hosts by providing a protective function against pathogenic viruses. The evidence for the endogenous TSE virus model and for the antiviral protective function of PrP is strong, and they are fully open to additional experimental testing. The endogenous virus model opens the TSE research field to new interpretations and directions, both in basic research and in associated biomedical and public health fields, and could lead to development of new diagnostic and therapeutic approaches

The Origin and Evolution of Viruses as Molecular Organisms

Viruses are the most abundant life forms and the repertoire of viral genes is greater than that of cellular genes. It is also evident that viruses have played a major role in driving cellular evolution, and yet, viruses are not part of mainstream biology, nor are they included in the Tree of Life. A reason for this major paradox in biology is the misleading dogma of viruses as viral particles and their enigmatic evolutionary origin. This article presents an alternative view about the nature of viruses based on their properties during the intracellular stage of their life cycle, when viruses express features comparable to those of many parasitic cellular species. Supporting this view about the nature of viruses is a novel hypothetical evolutionary model for their origin from parasitic cellular species that fused with their host cells. By losing their membrane and cellular structure within the host cell, these new types of parasitic species gained full access to precursors for the synthesis of their specific molecules and to the host’s information processing machineries, such as translation, which created unique parasitic and evolutionary opportunities. To identify viruses during their intracellular stage of their life cycle, in which their specific molecules are free or dispersed within the host cell, this paper introduces the concept of “molecular structure” and labels viruses as “molecular organisms.” Among the extant viruses, the life cycle of poxviruses and other complex viruses that fuse with their host cells provides compelling evidence for the fusion model. One of the most remarkable implications of fusion model is that new viral lineages originated from parasitic cellular species throughout the history of life, and that this process might still be active. Surprisingly, it appears that several parasitic cellular species are currently evolving into molecular organisms. More remarkably though, according to this model, several parasites that are currently classified as cellular organisms are in fact genuine molecular organisms. The current evidence for the fusion hypothesis is strong and it is fully testable using both experimental and phylogenetic approaches. The academic and research implications of this model, which supports the inclusion of viruses in the Tree of Life, are highly significant. Some of these implications are discussed in more detail in two other articles of this series, which presents a unifying model for the origin and evolution of cellular and viral domains, including the origin of life

A Unifying Scenario on the Origin and Evolution of Cellular and Viral Domains

The cellular theory on the nature of life has been one of the first major advancements in biology. Viruses, however, are the most abundant life forms, and their exclusion from mainstream biology and the Tree of Life (TOL) is a major paradox in biology. This article presents a broad, unifying scenario on the origin and evolution of cellular and viral domains that challenges the conventional views about the history of life and supports a TOL that includes viruses. Co-evolution of viruses and their host cells has led to some of the most remarkable developments and transitions in the evolution of life, including the origin of non-coding DNA as a genomic protective device against viral insertion damage. However, one of the major fundamental evolutionary developments driven by viruses was probably the origin of cellular domains - Bacteria, Archaea and Eukarya - from the Last Universal Common Ancestor (LUCA) lineage, by evolving anti-fusion mechanisms. Consistent with a novel fusion/fission model for the population mode of evolution of LUCA, this paper presents a “cell-like world” model for the origin of life. According to this model the evolution of coupled replication, transcription and translation system (RT&T) occurred within non-living cell-like compartments (CCs). In this model, the ancestral ribosome originated as template-based RNA synthesizing machinery. The origin of the cellular genome as a centralized unit for storage and replication of genetic information within the CCs facilitated the evolution of the ancestral ribosome into a powerful translation machinery - the modern ribosome. After several hundred millions of years of providing an enclosed environment and fusion/fission based exchanges necessary for the population mode of evolution of the basic metabolism and the RT&T, the CCs evolved into the first living entities on earth - the LUCA lineage. The paper concludes with a proposal for a TOL that integrates the co-evolution of cellular and viral domains. This is one of a series of three articles that present a unifying scenario on the origin and evolution of viral and cellular domains, including the origin of life, which has significant t bio-medical implications and could lead to a significant paradigm shift in biology

Epidemiología y relaciones evolutivas entre cepas de HIV subtipo F rumano y brasileño

La clasificación inicial del virus del HIV-1 como las cepas Africanas u Occidentales han sido reemplazadas por la subtipificación filogenética que usa datos de secuencia de nucleótidos. En HIV-1 han sido definidos ocho linajes o subtipos distintos de A a H. Considerando que el valor de la evolución del genoma del HIV-1 se estima en 0,5% a 1% al año y que la distancia genética promedio entre los subtipos de HIV-1 es aproximadamente 20%, es probable que estos subtipos se originaran antes de la pandemia del HIV-1. El mosaico global de los subtipos del HIV-1 es consistente con la hipótesis que la mayoría de las epidemias regionales comenzaron con la introducción de uno o de unas pocas variantes que se diversificaron localmente más que mediante olas radiantes de subtipos de HIV-1 ya diversificados que se diseminaron desde el lugar de origen. En este informe, nos abocamos a las relaciones evolutivas epidemiológicas entre el subtipo F del virus del HIV-1 recientemente identificados en dos regiones geográficamente distintas, Rumania y Brasil.Facultad de Ciencias Veterinaria

Epidemiología y relaciones evolutivas entre cepas de HIV subtipo F rumano y brasileño

La clasificación inicial del virus del HIV-1 como las cepas Africanas u Occidentales han sido reemplazadas por la subtipificación filogenética que usa datos de secuencia de nucleótidos. En HIV-1 han sido definidos ocho linajes o subtipos distintos de A a H. Considerando que el valor de la evolución del genoma del HIV-1 se estima en 0,5% a 1% al año y que la distancia genética promedio entre los subtipos de HIV-1 es aproximadamente 20%, es probable que estos subtipos se originaran antes de la pandemia del HIV-1. El mosaico global de los subtipos del HIV-1 es consistente con la hipótesis que la mayoría de las epidemias regionales comenzaron con la introducción de uno o de unas pocas variantes que se diversificaron localmente más que mediante olas radiantes de subtipos de HIV-1 ya diversificados que se diseminaron desde el lugar de origen. En este informe, nos abocamos a las relaciones evolutivas epidemiológicas entre el subtipo F del virus del HIV-1 recientemente identificados en dos regiones geográficamente distintas, Rumania y Brasil.Facultad de Ciencias Veterinaria

Epidemiología y relaciones evolutivas entre cepas de HIV subtipo F rumano y brasileño

La clasificación inicial del virus del HIV-1 como las cepas Africanas u Occidentales han sido reemplazadas por la subtipificación filogenética que usa datos de secuencia de nucleótidos. En HIV-1 han sido definidos ocho linajes o subtipos distintos de A a H. Considerando que el valor de la evolución del genoma del HIV-1 se estima en 0,5% a 1% al año y que la distancia genética promedio entre los subtipos de HIV-1 es aproximadamente 20%, es probable que estos subtipos se originaran antes de la pandemia del HIV-1. El mosaico global de los subtipos del HIV-1 es consistente con la hipótesis que la mayoría de las epidemias regionales comenzaron con la introducción de uno o de unas pocas variantes que se diversificaron localmente más que mediante olas radiantes de subtipos de HIV-1 ya diversificados que se diseminaron desde el lugar de origen. En este informe, nos abocamos a las relaciones evolutivas epidemiológicas entre el subtipo F del virus del HIV-1 recientemente identificados en dos regiones geográficamente distintas, Rumania y Brasil.Facultad de Ciencias Veterinaria

Dual and recombinant infections: an integral part of the HIV-1 epidemic in Brazil.

We systematically evaluated multiple and recombinant infections in an HIV-infected population selected for vaccine trials. Seventy-nine HIV-1 infected persons in a clinical cohort study in Rio de Janeiro, Brazil, were evaluated for 1 year. A combination of molecular screening assays and DNA sequencing showed 3 dual infections (3.8%), 6 recombinant infections (7.6%), and 70 (88.6%) infections involving single viral subtypes. In the three dual infections, we identified HIV-1 subtypes F and B, F and D, and B and D; in contrast, the single and recombinant infections involved only HIV-1 subtypes B and F. The recombinants had five distinct B/F mosaic patterns: Bgag-p17/Bgag-p24/Fpol/Benv, Fgag-p17/Bgag-p24/Fpol/Fenv, Bgag-p17/B-Fgag-p24/Fpol/Fenv, Bgag-p17/B-Fgag-p24/Fpol/Benv, and Fgag-p17/B-Fgag-p24/Fpol/Fenv. No association was found between dual or recombinant infections and demographic or clinical variables. These findings indicate that dual and recombinant infections are emerging as an integral part of the HIV/AIDS epidemic in Brazil and emphasize the heterogenous character of epidemics emerging in countries where multiple viral subtypes coexist