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A genome-wide analysis of the host a...

Rubins, Kathleen Hallisey.

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A genome-wide analysis of the host and viral responses during poxvirus infection.

Record Type:	Electronic resources : Monograph/item
Title/Author:	A genome-wide analysis of the host and viral responses during poxvirus infection./
Author:	Rubins, Kathleen Hallisey.
Description:	247 p.
Notes:	Source: Dissertation Abstracts International, Volume: 66-11, Section: B, page: 5801.
Contained By:	Dissertation Abstracts International66-11B.
Subject:	Biology, Microbiology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3197502
ISBN:	9780542432002

A genome-wide analysis of the host and viral responses during poxvirus infection.
Rubins, Kathleen Hallisey.

A genome-wide analysis of the host and viral responses during poxvirus infection. - 247 p.

Source: Dissertation Abstracts International, Volume: 66-11, Section: B, page: 5801.

Thesis (Ph.D.)--Stanford University, 2006.

Smallpox (variola virus) has played an unparalleled role in human history and remains a significant potential threat to public health. Variola and the related monkeypox (MPX) and vaccinia (VAC) viruses possess a variety of potential mechanisms for disrupting host immune responses. To improve our understanding of poxvirus pathogenesis and host-pathogen interactions, we examined the molecular and cellular features of different poxvirus infections in vivo in cynomolgus macaques, and in vitro in different cell types. Using cDNA microarrays, we compared the transcriptional changes induced with smallpox infection to the host transcriptional response to Ebola, an unrelated virus. We identified both conserved and relatively specific features of the host immune response to poxviruses and filoviruses and evidence for viral modulation of the host immune response. We designed a specialized microarray to detect simultaneously all MPX and VAC genes in addition to >18,000 host genes and characterized the host and viral gene expression patterns during in vitro infections in primary human fibroblasts, primary human macrophages and HeLa cells. Viral suppression of the host interferon response in vitro, as well as repression of exogenously-stimulated specific immune responses was demonstrated; however the host cells retained their capacity to respond to external stimuli, and host transcriptional differences between uninfected and infected cells were minimal. We also developed a map of the entire transcriptome of both MPX and VAC during infection, enabling us to compare viral gene expression across species, and determine expression patterns of previously uncharacterized ORFs. The viral transcriptomes showed a distinct temporal regulation and species-specific expression of viral gene subsets. These results represent the first picture of global gene expression responses for both viral and host genomes during smallpox, MPX and VAC infection, and provide new insights into possible virulence and host defense mechanisms for these important human pathogens.

ISBN: 9780542432002Subjects--Topical Terms:

1017734
Biology, Microbiology.

A genome-wide analysis of the host and viral responses during poxvirus infection.
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245 1 2 $a A genome-wide analysis of the host and viral responses during poxvirus infection.
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500 $a Source: Dissertation Abstracts International, Volume: 66-11, Section: B, page: 5801.
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502 $a Thesis (Ph.D.)--Stanford University, 2006.
520 $a Smallpox (variola virus) has played an unparalleled role in human history and remains a significant potential threat to public health. Variola and the related monkeypox (MPX) and vaccinia (VAC) viruses possess a variety of potential mechanisms for disrupting host immune responses. To improve our understanding of poxvirus pathogenesis and host-pathogen interactions, we examined the molecular and cellular features of different poxvirus infections in vivo in cynomolgus macaques, and in vitro in different cell types. Using cDNA microarrays, we compared the transcriptional changes induced with smallpox infection to the host transcriptional response to Ebola, an unrelated virus. We identified both conserved and relatively specific features of the host immune response to poxviruses and filoviruses and evidence for viral modulation of the host immune response. We designed a specialized microarray to detect simultaneously all MPX and VAC genes in addition to >18,000 host genes and characterized the host and viral gene expression patterns during in vitro infections in primary human fibroblasts, primary human macrophages and HeLa cells. Viral suppression of the host interferon response in vitro, as well as repression of exogenously-stimulated specific immune responses was demonstrated; however the host cells retained their capacity to respond to external stimuli, and host transcriptional differences between uninfected and infected cells were minimal. We also developed a map of the entire transcriptome of both MPX and VAC during infection, enabling us to compare viral gene expression across species, and determine expression patterns of previously uncharacterized ORFs. The viral transcriptomes showed a distinct temporal regulation and species-specific expression of viral gene subsets. These results represent the first picture of global gene expression responses for both viral and host genomes during smallpox, MPX and VAC infection, and provide new insights into possible virulence and host defense mechanisms for these important human pathogens.
590 $a School code: 0212.
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