Endogenous retroviruses in the human genome sequence

Griffiths, David J

doi:10.1186/gb-2001-2-6-reviews1017

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Endogenous retroviruses in the human genome sequence

review-article

Author(s): David J Griffiths ¹ ^,

Publication date (Electronic): 5 June 2001

Journal: Genome Biology

Publisher: BioMed Central

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Abstract

The human genome contains many endogenous retroviral sequences, and these have been suggested to play important roles in a number of physiological and pathological processes. Can the draft human genome sequences help us to define the role of these elements more closely?

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Most cited references 20

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Positional cloning of the mouse retrovirus restriction gene Fv1.

P Tissier, G. Towers, Deborah Best … (1996)

Vertebrate evolution has taken place against a background of constant retrovirus infection, and much of the mammalian genome consists of endogenous retrovirus-like elements. Several host genes have evolved to control retrovirus replication, including Friend-virus-susceptibility-1, Fv1, on mouse chromosome 4 (refs 3, 4). The Fv1 gene acts on murine leukaemia virus at a stage after entry into the target cell but before integration and formation of the provirus. Although restriction is not absolute, Fv1 prevents or delays spontaneous or experimentally induced viral tumours. In vitro, Fv1 restriction leads to an apparent 50-1,000 fold reduction in viral titre. Genetic evidence implicates a direct interaction between the Fv1 gene product and a component of the viral preintegration complex, the capsid protein CA (refs 7-9). We have now cloned Fv1: the gene appears to be derived from the gag region of an endogenous retrovirus unrelated to murine leukaemia virus, implying that the Fv1 protein and its target may share functional similarities despite the absence of nucleotide-sequence homology.

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Evolutionary analyses of the human genome.

W Li, Z. Gu, H. Wang … (2001)

The completion of the human genome will greatly accelerate the development of a new branch of science--evolutionary genomics. We can now directly address important questions about the evolutionary history of human genes and their regulatory sequences. Computational analyses of the human genome will reveal the number of genes and repetitive elements, the extent of gene duplication and compositional heterogeneity in the human genome, and the extent of domain shuffling and domain sharing among proteins. Here we present some first glimpses of these features.

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Retroviral RNA identified in the cerebrospinal fluids and brains of individuals with schizophrenia.

Fredrik Karlsson, Todd J. McArthur, Nicolas W J Schröder … (2001)

Schizophrenia is a serious brain disease of uncertain etiology. A role for retroviruses in the etiopathogenesis of some cases of schizophrenia has been postulated on the basis of clinical and epidemiological observations. We found sequences homologous to retroviral pol genes in the cell-free cerebrospinal fluids (CSFs) of 10 of 35 (29%) individuals with recent-onset schizophrenia or schizoaffective disorder. Retroviral sequences also were identified in the CSFs of 1 of 20 individuals with chronic schizophrenia. However, retroviral sequences were not identified in any of the CSFs obtained from 22 individuals with noninflammatory neurological diseases or from 30 individuals without evidence of neurological or psychiatric diseases (chi(2) = 19.25, P < 0.001). The nucleotide sequences identified in the CSFs of the individuals with schizophrenia or schizoaffective disorder were related to those of the human endogenous retroviral (HERV)-W family of endogenous retroviruses and to other retroviruses in the murine leukemia virus genus. Transcription of RNA homologous to members of the HERV-W family of retroviruses also was found to be up-regulated differentially in the frontal cortex regions of brains obtained postmortem from individuals with schizophrenia, as compared with corresponding tissue from individuals without psychiatric diseases. The transcriptional activation of certain retroviral elements within the central nervous system may be associated with the development of schizophrenia in at least some individuals. The further characterization of retroviral elements within the central nervous system of individuals with schizophrenia might lead to improved methods for the diagnosis and management of this disorder.

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Author and article information

Journal

Journal ID (nlm-ta): Genome Biol

Title: Genome Biology

Publisher: BioMed Central (London )

ISSN (Print): 1465-6906

ISSN (Electronic): 1465-6914

Publication date (Print): 2001

Publication date (Electronic): 5 June 2001

Volume: 2

Issue: 6

Pages: reviews1017.1-reviews1017.5

Affiliations

[1 ]Wohl Virion Centre, Department of Immunology and Molecular Pathology, Windeyer Institute of Medical Sciences, University College London, Cleveland Street, London W1T 4JF, UK. E-mail: d.j.griffiths@ucl.ac.uk

Article

Publisher ID: gb-2001-2-6-reviews1017

DOI: 10.1186/gb-2001-2-6-reviews1017

PMC ID: 138943

PubMed ID: 11423012

SO-VID: 12e30c42-ed97-48a2-87ab-5fd1d03df985

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