Endogenous retroviruses

Sheep betaretroviruses offer a unique model system to study the complex interaction between retroviruses and their host. Jaagsiekte sheep retrovirus (JSRV) is a pathogenic exogenous retrovirus and the causative agent of ovine pulmonary adenocarcinoma. The sheep genome contains at least 27 copies of endogenous retroviruses (enJSRVs) highly related to JSRV. enJSRVs have played several roles in the evolution of the domestic sheep as they are able to block the JSRV replication cycle and play a critical role in sheep conceptus development and placental morphogenesis. Available data strongly suggest that some dominant negative enJSRV proviruses (i.e. able to block JSRV replication) have been positively selected during evolution. Interestingly, viruses escaping the transdominant enJSRV loci have recently emerged (less than 200 years ago). Thus, endogenization of these retroviruses may still be occurring today. Therefore, sheep provide an exciting and unique system to study retrovirus-host coevolution. (Part of a Multi-author Review)     

Endogenous retroviruses

Xenotransplantation is defined by the PHS as any procedure that involves the transplantation, implantation or infusion into a human recipient of either (a) live cells, tissues or organs from a nonhuman animal source, or (b) human body fluids, cells, tissues or organs that have had ex vivo contact with live nonhuman animal cells, tissues or organs (Public Health Service Guideline on Infectious Disease Issues in Xenotransplantation). Use of pigs for human xenotransplantation raises concerns about the risks of transfer of infectious agents from the pig cells to xenotransplantation recipients. The observation that the porcine germline harbors genetic loci encoding porcine endogenous retroviruses (PERVs) that are in some cases infectious for human cells has resulted in renewed scientific interest in PERVs. However, in spite of the past 10 years of investigation, the actual risk for PERV infection, replication, and pathogenic outcome in human recipients of xenotransplantation products is still undefined. (Part of a Multi-author Review)     

Endogenous retroviruses

Up to 10% of the mouse genome is comprised of endogenous retrovirus (ERV) sequences, and most represent the remains of ancient germ line infections. Our knowledge of the three distinct classes of ERVs is inversely correlated with their copy number, and their characterization has benefited from the availability of divergent wild mouse species and subspecies, and from ongoing analysis of the Mus genome sequence. In contrast to human ERVs, which are nearly all extinct, active mouse ERVs can still be found in all three ERV classes. The distribution and diversity of ERVs has been shaped by host-virus interactions over the course of evolution, but ERVs have also been pivotal in shaping the mouse genome by altering host genes through insertional mutagenesis, by adding novel regulatory and coding sequences, and by their co-option by host cells as retroviral resistance genes. We review mechanisms by which an adaptive coexistence has evolved. (Part of a Multiauthor Review)     

Endogenous retroviruses

The genomes of vertebrates contain sequences that are similar to present-day exogenous retroviruses. Such sequences, called endogenous retroviruses (ERVs), have resulted from ancestral germ line infections by exogenous retroviruses which have thereafter been transmitted in a Mendelian fashion. By analogy to exogenous tumorigenic retroviruses, ERVs have been implicated in the pathogenesis of cancer. Cumulative evidence from animal models indicates that ERVs may participate in the process of malignant transformation or promote tumor growth, e.g. through insertional mutagenesis or via counteracting tumor immunosurveillance. Here, we review the role of ERVs in tumorigenesis with focus on human ERVs (HERVs) in human cancer. Although available data suggest a potential role of HERVs in human cancers, in particular germ cell tumors, the contributions of HERVs to human tumorigenesis warrant further elucidation. (Part of a Multi-author Review)     

Endogenous retroviruses

Endogenous retroviruses (ERVs) most likely are remnants of ancient retroviral infections. ERVs preserve functions of exogenous retroviruses to a varying extent, and can be parasites, symbionts or more or less neutral genetic ‘junk’.Their evolution has two facets, pre- and post-endogenization. Although the two are not clearly separated, the first pertains to retroviral evolution in general and the second to the fate of repetitive DNA and the evolution of the host organism and its genome. The study of ERVs provides much material for the understanding of retroviral evolution. This sequence archive reflects the history of successes and shortcomings of antiviral resistance, but also of strategic evolutionary decisions regarding genome organization and new gene acquisition. This review discusses retroviral evolution illustrated through HERVs, bioinformatic prerequisites for ERV studies, the endogenization process and HERV evolution post-endogenization, including relation to disease. (Part of a Multi-author Review)     

Integration target site selection for retroviruses and transposable elements

When a retrovirus infects a cell, its RNA genome is reverse transcribed into a double-stranded DNA, which is then permanently integrated into the host chromosome. Integration is one of the essential steps in the retroviral life cycle. Many transposable elements also move around and integrate into the host genome as part of their life cycle, some through RNA intermediates and some through 'cut and paste' mechanisms. Integration of retroviruses and transposable elements into 'sensitive areas' of the genome can cause irreparable damage. On the other hand, because of their ability to integrate permanently, and the relatively efficient rates of transgenesis, retroviruses and transposable elements are widely used as gene delivery tools in basic research and gene therapy trials. Recent events in gene therapy treatments for X-linked severe combined immunity deficiencies (X-SCID) have highlighted both the promise and some of the risks involved with utilizing retroviruses. Nine of 11 children were successfully treated for X-SCID using a retrovirus carrying the gene mutated in this disease. However, later two of these children developed leukemias because of retroviral integrations in the putative oncogene LMO2 [1]. A third child has also been demonstrated to have an integration in LMO2, but is as of yet nonsymptomatic [2]. It is a bit difficult to explain the high frequency of integrations into the same gene using a random model of retroviral integration, and there has been evidence for decades that retroviral integrations may not be random. But the data were somewhat limited in their power to determine the precise nature of the integration biases. The completion of the human genome sequence coupled with sensitive polymerase chain reaction techniques and an ever-decreasing cost of sequencing has given a powerful new tool to the study of integration site selection. In this review, we describe the findings from several recent global surveys of target site selection by retroviruses and transposable elements, and discuss the possible ramifications of these findings to both mechanisms of action and to the use of these elements as gene therapy vectors.     

Endogenous inhibitor of ecdysone synthesis in crabs

Summary Attempts to isolate the molt-inhibiting hormone (MIH) of crustaceans from crab eyestalks (ES) resulted in the characterization of xanthurenic acid as an inhibitor of ecdysone biosynthesis in the cultured Y-organ-complex (YOC) homogenate. It was also found that 3-hydroxyl-l-kynurenine present in the ES is transformed into xanthurenic acid in the YOC and body fluid. Its mode of inhibitory action in ecdysone biosynthesis is probably inactivation of cytochrome P-450.Acknowledgments. We thank Prof. M. Oka (Nagasaki University) and Dr J. Cappuzo (Oceanographic Inst.) for information on Y-organ and molting stages, Dr J. Termini and Mr J. Cesarelli (Columbia University) for organ excision of blue crabs and experiments in the early stage of this study, the Japan Sea Farming Association for aqua culture of crabs, Prof. Y. Umebachi (Kanazawa University) for a gift of 3-OH-l-Kyn, and Mr J. Rudloe (Gulf Specimen Co.) for collection and shipping of some selected crabs. This study was partially supported by NIH grant AI 10 187 (to K. N., at Columbia University).     

Endogenous recovery from colchicine-induced inhibition of growth

Fésumé Des doses de colchicine inférieures au seuil de son activité mutagénique sont à l'origine de la variation périodique du taux de croissance in vivo de la coléoptile de blé. En particulier, le comportement oscillatoire de cette régénération endogène a lieu dans un milieu qui contient la colchicine pendant toute la durée de l'incubation.

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Acknowledgments. This work has been partly done at the Department of Plant Science, University of Manitoba, Winnipeg, Manitoba, Canada. A research grant from the National Research Council of Canada is gratefully acknowleged.     

Endogenous inhibitor of ecdysone synthesis in crabs

Attempts to isolate the molt-inhibiting hormone (MIH) of crustaceans from crab eyestalks (ES) resulted in the characterization of xanthurenic acid as an inhibitor of ecdysone biosynthesis in the cultured Y-organ-complex (YOC) homogenate. It was also found that 3-hydroxy-L-kynurenine present in the ES is transformed into xanthurenic acid in the YOC and body fluid. Its mode of inhibitory action in ecdysone biosynthesis is probably inactivation of cytochrome P-450.     

Endogenous synthesis of lipid yolk in mosquito oocytes

Summary Morphological and physiological evidence indicate that lipid yolk in the mosquito is synthesized only within the oocyte within dense fields of free ribosomes. It does not come from the fat body or any other exogenous source.We are grateful to Dr A. L. Steinhauer for his support. Scientific article No. A2373, contribution No. 5388 of the Maryland Agricultural Experiment Station.     

Endogenous suppression of pheromone production in virgin female moths

Summary Sexual receptivity generally is reduced in moths after mating. We found that even in virginHeliothis zea females the titer of pheromone declines after the third night of adult life, although the number of eggs laid increases. Reduction in pheromone titer is not due to reduced amounts of pheromone biosynthesis activating neuropeptide. We have discovered that a substance present in the bursa, ovaries and hemolymph of senescing virgins suppresses pheromone production. A similar factor was found in 2-day-old mated females indicating that both virgin and mated females use this factor to suppress pheromone production.     

Endogenous splenic colonies and megakaryopoiesis in methylcellulose treated irradiated mice

Endogenous splenic colonies are increased in methylcellulose-treated irradiated mice, 10 days after sublethal irradiation (450 R). The spleen shows an enhancement of megakaryopoiesis, especially localized around foam-cell foci. This suggests that the macrophage system, activated through phagocytic activity against methylcellulose, affects megakaryopoiesis by a microenvironmental mechanism.     

Endogenous glucose release stimulated by oral sucrose administration in rats

Résumé On a examiné l'élevation de la glycémie chez les rats des 2 sexes après administration orale de sucrose. Une sécrétion de glucose semble prendre place en même temps que l'absorption de cette substance. On suggère un mécanisme basé sur l'interaction du glucagon, du glucose-6-phosphate et de l'insuline suivant l'administration de sucre. Les expériences témoins semblent éliminer la possibilité que ces résultats soient dus au stress.