Medicine and Health Sciences Commons^™

Whole-Genome Sequencing Of Kshv From Zambian Kaposi’S Sarcoma Biopsies Reveals Unique Viral Diversity, Landon N. Olp, Adrien Jeanniard, Clemence Marimo, John T. West, Charles Wood

Nebraska Center for Virology: Faculty Publications

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent for Kaposi’s sarcoma (KS). Both KSHV and KS are endemic in sub-Saharan Africa where approximately 84% of global KS cases occur. Nevertheless, whole-genome sequencing of KSHV has only been completed using isolates from Western countries—where KS is not endemic. The lack of whole-genome KSHV sequence data from the most clinically important geographical region, sub-Saharan Africa, represents an important gap as it remains unclear whether genomic diversity has a role on KSHV pathogenesis. We hypothesized that distinct KSHV genotypes might be present in sub-Saharan Africa compared to Western countries. Using a KSHV-targeted enrichment …

Effects Of Antiretroviral Therapy On Kaposi’S Sarcoma–Associated Herpesvirus (Kshv) Transmission Among Hiv-Infected Zambian Children, Landon Olp, Veenu Minhas, Clement Gondwe, Chipepo Kankasa, Janet M. Wojcicki, Charles Mitchell, John T. West, Charles Wood

Nebraska Center for Virology: Faculty Publications

Background: The risk of Kaposi’s sarcoma–associated herpesvirus (KSHV) acquisition among children is increased by HIV infection. Antiretroviral therapy (ART) was recently made widely available to HIV-infected children in Zambia. However, the impact of early ART on KSHV transmission to HIV-infected children is unknown.

Methods: We enrolled and followed a cohort of 287 HIV-exposed, KSHV-negative children under 12 months of age from Lusaka, Zambia, to identify KSHV seroconversion events. Potential factors associated with KSHV infection—with an emphasis on HIV, ART, and immunological measures—were assessed through structured questionnaires and blood analyses. Incidence rate, Kaplan- Meier, and multivariable Cox regression models were used …

Bovine Herpesvirus 1 Productive Infection Stimulates Inflammosome Formation And Caspase 1 Activity, Jianlin Wang, Jeffrey Alexander, Matthew S. Wiebe, Clinton J. Jones

Nebraska Center for Virology: Faculty Publications

Bovine herpesvirus 1 (BoHV-1), a significant viral pathogen of cattle, causes inflammation in affected tissue during acute infection. Consequently, we tested whether productively infected bovine cells stimulate inflammasome formation. Expression of two components required for inflammasome formation, the DNA sensor IFI16 (gamma-interferon-inducible protein 16) and NLRP3 (NOD-like receptor family, pyrin domain containing 3), were induced in bovine kidney cells by eight hours after infection. IFI16 was detected in punctate granules localized to the cytoplasm and nucleus. During productive infection, more than ten times more cells were caspase 1 positive, which is activated following inflammasome formation. Two caspase 1 inhibitors had …

Siv Infection Induces Accumulation Of Plasmacytoid Dendritic Cells In The Gut Mucosa, R. Keith Reeves, Tristan I. Evans, Jacqueline Gillis, Fay E. Wong, Guobin Kang, Qingsheng Li, R. Paul Johnson

Nebraska Center for Virology: Faculty Publications

Multiple studies suggest that plasmacytoid dendritic cells (pDCs) are depleted and dysfunctional during human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) infection, but little is known about pDCs in the gut—the primary site of virus replication. Here, we show that during SIV infection, pDCs were reduced 3-fold in the circulation and significantly upregulated the gut-homing marker α4β7, but were increased 4-fold in rectal biopsies of infected compared to naive macaques. These data revise the understanding of pDC immunobiology during SIV infection, indicating that pDCs are not necessarily depleted, but instead may traffic to and accumulate in the gut mucosa.

Aids-Associated Viral Oncogenesis: Overview, Charles Wood

Nebraska Center for Virology: Faculty Publications

It has been 25 years since the acquired immunodeficiency syndrome (AIDS) was first described and over 23 years since the human immunodeficiency virus (HIV) associated with the disease was first discovered. In spite of the tremendous progress that was made in understanding both the disease and the virus, there are still millions of people infected, died, or living with the disease. As for the year 2005 alone, the Joint United Nations Programme on HIV/AIDS (http://www.UNAIDS.org) estimates that there are about 40 million people living with HIV/AIDS globally, and approximately 3 million people died from AIDS in the year. Globally, it …

The Vaccinia-Related Kinases Phosphorylate The N' Terminus Of Baf, Regulating Its Interaction With Dna And Its Retention In The Nucleus, R. Jeremy Nichols, Matthew S. Wiebe, Paula Traktman

Nebraska Center for Virology: Faculty Publications

The vaccinia-related kinases (VRKs) comprise a branch of the casein kinase family whose members are characterized by homology to the vaccinia virus B1 kinase. The VRK orthologues encoded by Caenorhabditis elegans and Drosophila melanogaster play an essential role in cell division; however, substrates that mediate this role have yet to be elucidated. VRK1 can complement the temperature sensitivity of a vaccinia B1 mutant, implying that VRK1 and B1 have overlapping substrate specificity. Herein, we demonstrate that B1, VRK1, and VRK2 efficiently phosphorylate the extreme N' terminus of the BAF protein (Barrier to Autointegration Factor). BAF binds to both DNA and …

Construction And Characterization Of A Chimeric Virus (Biv/Hiv-1) Carrying The Bovine Immunodeficiency Virus Gag-Pol Gene: Research Letters, Guomin Chen, Shuhui Wang, Kun Xiong, Jinzhong Wang, Tao Ye, Wenping Dong, Qi Wang, Qimin Chen, Yunqi Geng, Charles Wood, Yi Zeng

Nebraska Center for Virology: Faculty Publications

HIV-1HXB2 5′LTR region, most of BIVR29 gag-pol segment and HIV-1HXB2 pol IN-3′LTR region were respectively amplified. A chimeric clone, designated as pHBIV₃₇₅₃, was constructed by cloning three fragments sequentially into pUC18. MT4 cells were transfected with pHBIV₃₇₅₃. The replication and expressions of the chimeric virus (HBIV₃₇₅₃) were monitored by RT activity and IFA. The results firstly demonstrated that it is possible to generate a new type of the BIV/HIV-1 chimeric virus containing BIV gag-pol gene.

Vertical Transmission Of Kaposi's Sarcoma-Associated Herpesvirus, Hamakwa Mantina, Chipepo Kankasa, Winslow Klaskala, Brad Brayfield, James Campbell, Quijiang Du, Ganapati Bhat, Francis Kasolo, Charles Mitchell, Charles Wood

Nebraska Center for Virology: Faculty Publications

Little is presently known about the specific routes of transmission of Kaposi’s sarcoma-associated herpesvirus (KSHV) or human herpesvirus-8 (HHV-8). To investigate whether this agent might be transmitted vertically from mother to infant, we conducted a study on 89 KSHV seropositive mothers and their newborn infants. Thirteen mothers (14.6%) had KSHV DNA detected in their peripheral blood mononuclear cells (PBMC). Two of 89 samples drawn at birth from infants born to KSHV seropositive mothers had KSHV DNA detectable within their PBMC. These findings suggest that KSHV can be transmitted perinatally, but infrequently. Other routes of transmission such as horizontal transmission remain …