Abstract:
:Kaposi sarcoma-associated herpesvirus (KSHV) is an emerging pathogen and is the causative infectious agent of Kaposi sarcoma and two malignancies of B cell origin. To date, there is no licensed KSHV vaccine. Development of an effective vaccine against KSHV continues to be limited by a poor understanding of how the virus initiates acute primary infection in vivo in diverse human cell types. The role of glycoprotein H (gH) in herpesvirus entry mechanisms remains largely unresolved. To characterize the requirement for KSHV gH in the viral life cycle and in determination of cell tropism, we generated and characterized a mutant KSHV in which expression of gH was abrogated. Using a bacterial artificial chromosome containing a complete recombinant KSHV genome and recombinant DNA technology, we inserted stop codons into the gH coding region. We used electron microscopy to reveal that the gH-null mutant virus assembled and exited from cells normally, compared to wild-type virus. Using purified virions, we assessed infectivity of the gH-null mutant in diverse mammalian cell types in vitro Unlike wild-type virus or a gH-containing revertant, the gH-null mutant was unable to infect any of the epithelial, endothelial, or fibroblast cell types tested. However, its ability to infect B cells was equivocal and remains to be investigated in vivo due to generally poor infectivity in vitro Together, these results suggest that gH is critical for KSHV infection of highly permissive cell types, including epithelial, endothelial, and fibroblast cells.IMPORTANCE All homologues of herpesvirus gH studied to date have been implicated in playing an essential role in viral infection of diverse permissive cell types. However, the role of gH in the mechanism of KSHV infection remains largely unresolved. In this study, we generated a gH-null mutant KSHV and provided evidence that deficiency of gH expression did not affect viral particle assembly or egress. Using the gH-null mutant, we showed that gH was indispensable for KSHV infection of epithelial, endothelial, and fibroblast cells in vitro This suggests that gH is an important target for the development of a KSHV prophylactic vaccine to prevent initial viral infection.
journal_name
J Viroljournal_title
Journal of virologyauthors
Muniraju M,Mutsvunguma LZ,Foley J,Escalante GM,Rodriguez E,Nabiee R,Totonchy J,Mulama DH,Nyagol J,Wussow F,Barasa AK,Brehm M,Ogembo JGdoi
10.1128/JVI.00630-19subject
Has Abstractpub_date
2019-07-30 00:00:00issue
16eissn
0022-538Xissn
1098-5514pii
JVI.00630-19journal_volume
93pub_type
杂志文章abstract::The human immunodeficiency virus type 1 (HIV-1) tat protein functions at a much lower level in rodent cells than in human cells. This species-specific difference in trans activation appears to be due to the lack of a functional homolog of a human cofactor for tat in rodent cells. Using HIV-1 long terminal repeat-drive...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.9.4565-4567.1990
更新日期:1990-09-01 00:00:00
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doi:10.1128/JVI.03233-12
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doi:10.1128/JVI.01324-18
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journal_title:Journal of virology
pub_type: 杂志文章,评审
doi:10.1128/JVI.00287-15
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02144-08
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.8.4744-4754.2005
更新日期:2005-04-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.3.1967-1973.1998
更新日期:1998-03-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.10.8303-8307.1999
更新日期:1999-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.75.17.8147-8157.2001
更新日期:2001-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.19.10357-10365.2003
更新日期:2003-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.52.2.680-682.1984
更新日期:1984-11-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.5.2910-2919.2005
更新日期:2005-03-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.44.3.804-812.1982
更新日期:1982-12-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.00958-12
更新日期:2012-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.7.2512-2515.1988
更新日期:1988-07-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.18.9378-9388.2002
更新日期:2002-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.29.2.612-623.1979
更新日期:1979-02-01 00:00:00
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doi:10.1128/JVI.44.1.366-373.1982
更新日期:1982-10-01 00:00:00
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pub_type: 杂志文章
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更新日期:1981-01-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.46.3.964-973.1983
更新日期:1983-06-01 00:00:00
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pub_type: 杂志文章
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更新日期:1982-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.4.2031-2036.1992
更新日期:1992-04-01 00:00:00
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pub_type: 杂志文章
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更新日期:2019-03-05 00:00:00
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pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.10.2956-2961.1987
更新日期:1987-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.8.5642-5645.1996
更新日期:1996-08-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.3.2163-2170.1997
更新日期:1997-03-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2008-11-01 00:00:00