Diss. (sammanfattning) Uppsala : Uppsala universitet, 2005. / Härtill 5 uppsatser.

BACKGROUND: Retroviruses infect a wide range of vertebrates. However, little is known about the diversity of retroviruses in basal vertebrates. Endogenous retrovirus (ERV) provides a valuable resource to study the ecology and evolution of retrovirus. FINDINGS: I performed a genome-scale screening for ERVs in the elephant shark (Callorhinchus milii) and identified three complete or nearly complete ERVs and many short ERV fragments. I designate these retroviral elements "C. milli ERVs" (CmiERVs). Phylogenetic analysis shows that the CmiERVs form three distinct lineages. The genome invasions by these retroviruses are estimated to take place more than 50 million years ago. CONCLUSIONS: My results reveal the extensive retroviral diversity in the elephant shark. Diverse retroviruses appear to have been associated with cartilaginous fishes for millions of years. These findings have important implications in understanding the diversity and evolution of retroviruses.

Endogenous retroviruses (ERVs) comprise a significant portion of the genome of all mammals and have been implicated in placental development in multiple species. The ovine genome contains approximately 27 copies of endogenous betaretroviruses (enJSRVs) that are related to the exogenous Jaagsiekte sheep retrovirus (JSRV), an oncogenic retrovirus tropic to the lung. The enJSRV loci are abundantly expressed in the female reproductive tract and the conceptus, and they are essential to conceptus development. Studies were conducted to determine: 1) the effect of exogenous progesterone administration on conceptus development after loss of enJSRV Env; 2) the specific enJSRV env expressed in the developing conceptus; and 3) if the uterus produces enJSRV viral particles that are capable of transducing the conceptus. Study One determined the effects of exogenous progesterone on development of the conceptus in which enJSRV Env was ablated. Despite rescuing conceptus survival, the conceptuses were morphologically fragile and had reduced binucleate cell (BNC) numbers. These results suggest that mononuclear trophectoderm cell (MTC) proliferation and differentiation is dependent on enJSRV Env, even in a uterine environment supported by exogenous progesterone. Study Two assessed the enJSRV loci transcribed in the ovine conceptus during elongation before (day 13) and after (day 18) onset of BNC differentiation. The most represented loci in both day 13 and day 18 conceptuses encoded truncated Env proteins that did not contain membrane-spanning domains. Conceptuses from both time points contained evidence of the transcription of full-length, biologically active enJSRV Env, as well as completely intact proviral loci with the ability to produce viral particles in vitro. Study Three utilized a transpecies embryo transfer experiment to determine if the intact enJSRVs loci could produce viral particles in vivo. The presence of enJSRV viral particles in the uterus was confirmed, as was their ability to transduce the conceptus. Collectively, these studies provide evidence of truncated Env proteins, intact biologically active Env proteins, and enJSRVs viral particles within the ovine uterus and conceptus that are necessary to stimulate proliferation and differentiation of MTCs even in a uterine environment supported by exogenous progesterone.

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Thesis (Ph. D.)--University of Washington, 1998. / Vita. Includes bibliographical references (leaves [154]-164).

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Diss. (sammanfattning) Uppsala : Univ., 2002. / Härtill 5 uppsatser.

Endogenous retroviruses (ERVs) originate by germline infection and subsequent mendelian inheritance of their exogenous counterparts. With notable exceptions, all mammalian ERVs are evolutionarily old and fixed in the population of its host species. Some groups of retroviruses were believed not to be able to form endogenous copies. We discovered an additional endogenous Lentivirus and a first endogenous Deltaretrovirus. Both of these groups were previously considered unable to form endogenous copies. Endogenous lentiviruses were discovered only recently and are still quite rare. These are still just small pieces of evidence insufficient to give a broader picture about the history of virus endogenization. We described a novel endogenous Lentivirus in the genome of Malayan colugo (Galeopterus variegatus) denoted ELVgv (endogenous Lentivirus of G. variegatus). Based on several analyses we proved that this is the oldest Lentivirus discovered up to date and confirmed its presence in the only other extant species of Dermoptera - Cynocephalus volans. Endogenous deltaretroviruses were the last group without a single endogenous member. We detected the remnants of endogenous Deltaretrovirus in the genome of Natal Long-fingered bat (Miniopterus natalensis). However, this sequence was present in the genome only in one...

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24524号 / 医博第4966号 / 新制||医||1065(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 齊藤 博英, 教授 萩原 正敏, 教授 山崎 渉 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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