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Article ; Online: Elevated iNOS and 3'-nitrotyrosine in Kaposi's Sarcoma tumors and mouse model.

Vladimirova, Olga / Soldan, Samantha / Su, Chenhe / Kossenkov, Andrew / Ngalamika, Owen / Tso, For Yue / West, John T / Wood, Charles / Lieberman, Paul M

Tumour virus research

2023 Volume 15, Page(s) 200259

Abstract: Kaposi's Sarcoma (KS) is a heterogenous, multifocal vascular malignancy caused by the human herpesvirus 8 (HHV8), also known as Kaposi's Sarcoma-Associated Herpesvirus (KSHV). Here, we show that KS lesions express iNOS/NOS2 broadly throughout KS lesions, ...

Abstract	Kaposi's Sarcoma (KS) is a heterogenous, multifocal vascular malignancy caused by the human herpesvirus 8 (HHV8), also known as Kaposi's Sarcoma-Associated Herpesvirus (KSHV). Here, we show that KS lesions express iNOS/NOS2 broadly throughout KS lesions, with enrichment in LANA positive spindle cells. The iNOS byproduct 3-nitrotyrosine is also enriched in LANA positive tumor cells and colocalizes with a fraction of LANA-nuclear bodies. We show that iNOS is highly expressed in the L1T3/mSLK tumor model of KS. iNOS expression correlated with KSHV lytic cycle gene expression, which was elevated in late-stage tumors (>4 weeks) but to a lesser degree in early stage (1 week) xenografts. Further, we show that L1T3/mSLK tumor growth is sensitive to an inhibitor of nitric oxide, L-NMMA. L-NMMA treatment reduced KSHV gene expression and perturbed cellular gene pathways relating to oxidative phosphorylation and mitochondrial dysfunction. These finding suggest that iNOS is expressed in KSHV infected endothelial-transformed tumor cells in KS, that iNOS expression depends on tumor microenvironment stress conditions, and that iNOS enzymatic activity contributes to KS tumor growth.
MeSH term(s)	Animals ; Humans ; Mice ; Antigens, Viral/genetics ; Herpesvirus 8, Human/genetics ; omega-N-Methylarginine ; Sarcoma, Kaposi/genetics ; Tumor Microenvironment
Chemical Substances	3-nitrotyrosine (3604-79-3) ; Antigens, Viral ; omega-N-Methylarginine (27JT06E6GR) ; NOS2 protein, human (EC 1.14.13.39) ; Nos2 protein, mouse (EC 1.14.13.39)
Language	English
Publishing date	2023-03-01
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2666-6790
ISSN (online)	2666-6790
DOI	10.1016/j.tvr.2023.200259
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Article ; Online: Viral Epitope Scanning Reveals Correlation between Seasonal HCoVs and SARS-CoV-2 Antibody Responses among Cancer and Non-Cancer Patients.

Lidenge, Salum J / Yalcin, Dicle / Bennett, Sydney J / Ngalamika, Owen / Kweyamba, Brenda B / Mwita, Chacha J / Tso, For Yue / Mwaiselage, Julius / West, John T / Wood, Charles

Viruses

2024 Volume 16, Issue 3

Abstract: Seasonal coronaviruses (HCoVs) are known to contribute to cross-reactive antibody (Ab) responses against SARS-CoV-2. While these responses are predictable due to the high homology between SARS-CoV-2 and other CoVs, the impact of these responses on ... ...

Abstract	Seasonal coronaviruses (HCoVs) are known to contribute to cross-reactive antibody (Ab) responses against SARS-CoV-2. While these responses are predictable due to the high homology between SARS-CoV-2 and other CoVs, the impact of these responses on susceptibility to SARS-CoV-2 infection in cancer patients is unclear. To investigate the influence of prior HCoV infection on anti-SARS-CoV-2 Ab responses among COVID-19 asymptomatic individuals with cancer and controls without cancers, we utilized the VirScan technology in which phage immunoprecipitation and sequencing (PhIP-seq) of longitudinal plasma samples was performed to investigate high-resolution (i.e., epitope level) humoral CoV responses. Despite testing positive for anti-SARS-CoV-2 Ab in the plasma, a majority of the participants were asymptomatic for COVID-19 with no prior history of COVID-19 diagnosis. Although the magnitudes of the anti-SARS-CoV-2 Ab responses were lower in individuals with Kaposi sarcoma (KS) compared to non-KS cancer individuals and those without cancer, the HCoV Ab repertoire was similar between individuals with and without cancer independent of age, sex, HIV status, and chemotherapy. The magnitudes of the anti-spike HCoV responses showed a strong positive association with those of the anti-SARS-CoV-2 spike in cancer patients, and only a weak association in non-cancer patients, suggesting that prior infection with HCoVs might play a role in limiting SARS-CoV-2 infection and COVID-19 disease severity.
MeSH term(s)	Humans ; SARS-CoV-2 ; Antibody Formation ; COVID-19 Testing ; Seasons ; COVID-19 ; Neoplasms ; Sarcoma, Kaposi ; Antibodies, Viral ; Epitopes ; Spike Glycoprotein, Coronavirus
Chemical Substances	Antibodies, Viral ; Epitopes ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2024-03-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v16030448
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Article ; Online: Reduction of Kaposi's Sarcoma-Associated Herpesvirus Latency Using CRISPR-Cas9 To Edit the Latency-Associated Nuclear Antigen Gene.

Tso, For Yue / West, John T / Wood, Charles

Journal of virology

2019 Volume 93, Issue 7

Abstract: Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS), an AIDS-defining cancer in HIV-1-infected individuals or immune-suppressed transplant patients. The prevalence for both KSHV and KS are highest in sub-Saharan ...

Abstract	Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS), an AIDS-defining cancer in HIV-1-infected individuals or immune-suppressed transplant patients. The prevalence for both KSHV and KS are highest in sub-Saharan Africa where HIV-1 infection is also epidemic. There is no effective treatment for advanced KS; therefore, the survival rate is low. Similar to other herpesviruses, KSHV's ability to establish latent infection in the host presents a major challenge to KS treatment or prevention. Strategies to reduce KSHV episomal persistence in latently infected cells might lead to approaches to prevent KS development. The CRISPR-Cas9 system is a gene editing technique that has been used to specifically manipulate the HIV-1 genome but also Epstein-Barr virus (EBV) which, similar to KSHV, belongs to the
MeSH term(s)	Animals ; Antigens, Viral/genetics ; CRISPR-Cas Systems/genetics ; Cell Line ; Chlorocebus aethiops ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; Endothelial Cells/virology ; Epithelial Cells/virology ; HEK293 Cells ; Herpesviridae Infections/virology ; Herpesvirus 8, Human/genetics ; Humans ; Nuclear Proteins/genetics ; Sarcoma, Kaposi/virology ; Vero Cells ; Virus Latency/genetics ; Virus Replication/genetics
Chemical Substances	Antigens, Viral ; Nuclear Proteins ; latency-associated nuclear antigen
Language	English
Publishing date	2019-03-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.02183-18
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Article ; Online: SARS-CoV-2-Specific T Cell Immunity in HIV-Associated Kaposi Sarcoma Patients in Zambia.

Ngalamika, Owen / Mukasine, Marie Claire / Kamanzi, Patrick / Kawimbe, Musonda / Mujajati, Aaron / Tso, For Yue / Lidenge, Salum J / Mumba, Chibamba

Journal of immunology research

2022 Volume 2022, Page(s) 2114285

Abstract: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) virus is the cause of coronavirus disease 2019 (COVID-19). It has caused millions of infections and deaths globally over a 2-year period. Some populations including those living with HIV ... ...

Abstract	Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) virus is the cause of coronavirus disease 2019 (COVID-19). It has caused millions of infections and deaths globally over a 2-year period. Some populations including those living with HIV and/or cancer are reported to be at a higher risk of infection and severe disease. HIV infection leads to a depletion of CD4
MeSH term(s)	Antibodies, Viral ; COVID-19 ; HIV Infections/drug therapy ; Humans ; Immunity, Cellular ; SARS-CoV-2 ; Sarcoma, Kaposi ; T-Lymphocytes ; Zambia/epidemiology
Chemical Substances	Antibodies, Viral
Language	English
Publishing date	2022-07-28
Publishing country	Egypt
Document type	Journal Article
ZDB-ID	2817541-4
ISSN	2314-7156 ; 2314-7156
ISSN (online)	2314-7156
ISSN	2314-7156
DOI	10.1155/2022/2114285
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Article ; Online: SARS-CoV-2-specific T cell and humoral immunity in individuals with and without HIV in an African population: a prospective cohort study.

Ngalamika, Owen / Lidenge, Salum J / Mukasine, Marie Claire / Kawimbe, Musonda / Kamanzi, Patrick / Ngowi, John R / Mwaiselage, Julius / Tso, For Yue

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases

2022 Volume 127, Page(s) 106–115

Abstract: Objectives: To longitudinally compare SARS-CoV-2-specific T cell and humoral immune responses between convalescent individuals who are HIV-positive (HIV+) and HIV-negative (HIV-).: Methods: We conducted enzyme-linked immunospots to determine the SARS- ...

Abstract	Objectives: To longitudinally compare SARS-CoV-2-specific T cell and humoral immune responses between convalescent individuals who are HIV-positive (HIV+) and HIV-negative (HIV-). Methods: We conducted enzyme-linked immunospots to determine the SARS-CoV-2-specific T cell responses to spike and nucleocapsid, membrane protein, and other open reading frame proteins (NMO), whereas an immunofluorescence assay was used to determine the humoral responses. Participants were sampled at baseline and after 8 weeks of follow-up. Results: Individuals who are HIV- had significantly more T cell responses to NMO and spike than individuals who are HIV+ at baseline, P-value = 0.026 and P-value = 0.029, respectively. At follow-up, T cell responses to NMO and spike in individuals who are HIV+ increased to levels comparable with individuals who are HIV-. T cell responses in the HIV- group significantly decreased from baseline levels at the time of follow-up (spike [P-value = 0.011] and NMO [P-value = 0.014]). A significantly higher number of individuals in the HIV+ group had an increase in T cell responses to spike (P-value = 0.01) and NMO (P-value = 0.026) during the follow-up period than the HIV- group. Antispike and antinucleocapsid antibody titers were high (1: 1280) and not significantly different between individuals who were HIV- and HIV+ at baseline. A significant decrease in antinucleocapsid titer was observed in the HIV- (P-value = 0.0001) and the HIV+ (P-value = 0.001) groups at follow-up. SARS-CoV-2 vaccination was more effective in boosting the T cell than antibody responses shortly after infection. Conclusion: There is an impairment of SARS-CoV-2-specific T cell immunity in individuals who are HIV+ with advanced immunosuppression. SARS-CoV-2-specific T cell immune responses may be delayed in individuals who are HIV+, even in those on antiretroviral therapy. There is no difference in SARS-CoV-2-specific humoral immunity between individuals who are HIV- and HIV+.
MeSH term(s)	Humans ; Immunity, Humoral ; COVID-19 ; COVID-19 Vaccines ; Prospective Studies ; SARS-CoV-2 ; T-Lymphocytes ; Antibodies, Viral
Chemical Substances	COVID-19 Vaccines ; Antibodies, Viral
Language	English
Publishing date	2022-12-11
Publishing country	Canada
Document type	Journal Article
ZDB-ID	1331197-9
ISSN	1878-3511 ; 1201-9712
ISSN (online)	1878-3511
ISSN	1201-9712
DOI	10.1016/j.ijid.2022.12.009
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Article ; Online: Co-infection and co-localization of Kaposi sarcoma-associated herpesvirus and Epstein-Barr virus in HIV-associated Kaposi sarcoma: a case report.

Julius, Peter / Kang, Guobin / Siyumbwa, Stepfanie / Musumali, Jane / Tso, For Yue / Ngalamika, Owen / Kaile, Trevor / Maate, Fred / Moonga, Phyllis / West, John T / Angeletti, Peter / Wood, Charles

Frontiers in cellular and infection microbiology

2023 Volume 13, Page(s) 1270935

Abstract: Kaposi sarcoma (KS), a multifocal vascular neoplasm frequently observed in HIV-positive individuals, primarily affects the skin, mucous membranes, visceral organs, and lymph nodes. KS is associated primarily with Kaposi sarcoma-associated herpesvirus ( ... ...

Abstract	Kaposi sarcoma (KS), a multifocal vascular neoplasm frequently observed in HIV-positive individuals, primarily affects the skin, mucous membranes, visceral organs, and lymph nodes. KS is associated primarily with Kaposi sarcoma-associated herpesvirus (KSHV) infection. In this case report, we present a rare occurrence of co-infection and co-localization of KSHV and Epstein-Barr virus (EBV) in KS arising from the conjunctiva, which, to our knowledge, has not been reported previously. Immunohistochemistry (IHC), DNA polymerase chain reaction (PCR), and EBV-encoded RNA
MeSH term(s)	Humans ; Sarcoma, Kaposi/complications ; Sarcoma, Kaposi/epidemiology ; Herpesvirus 8, Human/genetics ; Herpesvirus 4, Human ; Epstein-Barr Virus Infections/complications ; Coinfection/complications ; Herpesviridae Infections ; Acquired Immunodeficiency Syndrome/complications
Language	English
Publishing date	2023-10-20
Publishing country	Switzerland
Document type	Case Reports ; Research Support, N.I.H., Extramural
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2023.1270935
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Article ; Online: Longitudinal Variations in Antibody Responses against SARS-CoV-2 Spike Epitopes upon Serial Vaccinations.

Yalcin, Dicle / Bennett, Sydney J / Sheehan, Jared / Trauth, Amber J / Tso, For Yue / West, John T / Hagensee, Michael E / Ramsay, Alistair J / Wood, Charles

International journal of molecular sciences

2023 Volume 24, Issue 8

Abstract: The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacted healthcare, the workforce, and worldwide socioeconomics. Multi-dose mono- or bivalent mRNA vaccine regimens have shown high efficacy in protection ... ...

Abstract	The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacted healthcare, the workforce, and worldwide socioeconomics. Multi-dose mono- or bivalent mRNA vaccine regimens have shown high efficacy in protection against SARS-CoV-2 and its emerging variants with varying degrees of efficacy. Amino acid changes, primarily in the receptor-binding domain (RBD), result in selection for viral infectivity, disease severity, and immune evasion. Therefore, many studies have centered around neutralizing antibodies that target the RBD and their generation achieved through infection or vaccination. Here, we conducted a unique longitudinal study, analyzing the effects of a three-dose mRNA vaccine regimen exclusively using the monovalent BNT162b2 (Pfizer/BioNTech) vaccine, systematically administered to nine previously uninfected (naïve) individuals. We compare changes in humoral antibody responses across the entire SARS-CoV-2 spike glycoprotein (S) using a high-throughput phage display technique (VirScan). Our data demonstrate that two doses of vaccination alone can achieve the broadest and highest magnitudes of anti-S response. Moreover, we present evidence of novel highly boosted non-RBD epitopes that strongly correlate with neutralization and recapitulate independent findings. These vaccine-boosted epitopes could facilitate multi-valent vaccine development and drug discovery.
MeSH term(s)	Humans ; SARS-CoV-2 ; COVID-19/prevention & control ; Antibody Formation ; BNT162 Vaccine ; Longitudinal Studies ; Pandemics ; Vaccination ; Antibodies, Neutralizing ; Epitopes ; Antibodies, Viral
Chemical Substances	BNT162 Vaccine ; Antibodies, Neutralizing ; Epitopes ; Antibodies, Viral
Language	English
Publishing date	2023-04-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24087292
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Article ; Online: The Kaposi's Sarcoma-Associated Herpesvirus (KSHV) gH/gL Complex Is the Predominant Neutralizing Antigenic Determinant in KSHV-Infected Individuals.

Mortazavi, Yasaman / Lidenge, Salum J / Tran, Tara / West, John T / Wood, Charles / Tso, For Yue

Viruses

2020 Volume 12, Issue 3

Abstract: Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS), one of the most prevalent cancers of people living with HIV/AIDS in sub-Saharan Africa. The seroprevalence for KSHV is high in the region, and no ... ...

Abstract	Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS), one of the most prevalent cancers of people living with HIV/AIDS in sub-Saharan Africa. The seroprevalence for KSHV is high in the region, and no prophylactic vaccine against the virus is available. In this study, we characterized the antigenic targets of KSHV-specific neutralizing antibodies (nAbs) in asymptomatic KSHV-infected individuals and KS patients with high nAbs titers. We quantified the extent to which various KSHV envelope glycoproteins (gB, ORF28, ORF68, gH, gL, gM, gN and gpK8.1) adsorbed/removed KSHV-specific nAbs from the plasma of infected individuals. Our study revealed that plasma from a majority of KSHV neutralizers recognizes multiple viral glycoproteins. Moreover, the breadth of nAbs responses against these viral glycoproteins varies among endemic KS, epidemic KS and asymptomatic KSHV-infected individuals. Importantly, among the KSHV glycoproteins, the gH/gL complex, but neither gH nor gL alone, showed the highest adsorption of KSHV-specific nAbs. This activity was detected in 80% of the KSHV-infected individuals regardless of their KS status. The findings suggest that the gH/gL complex is the predominant antigenic determinant of KSHV-specific nAbs. Therefore, gH/gL is a potential target for development of KSHV prophylactic vaccines.
MeSH term(s)	Adult ; Aged ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Epitopes/immunology ; Female ; Genetic Vectors/genetics ; HEK293 Cells ; Herpesviridae Infections/immunology ; Herpesviridae Infections/virology ; Herpesvirus 8, Human/physiology ; Humans ; Male ; Middle Aged ; Sarcoma, Kaposi ; Viral Envelope Proteins/immunology ; Viral Load ; Young Adult
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Epitopes ; Viral Envelope Proteins
Language	English
Publishing date	2020-02-26
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v12030256
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Article: Lower SARS-CoV-2 Seroprevalence among Cancer Patients in Sub-Saharan Africa.

Tso, For Yue / Lidenge, Salum J / Ngowi, John R / Peña, Phoebe B / Clegg, Ashley A / Ngalamika, Owen / Mwita, Chacha J / Mwaiselage, Julius / Wood, Charles

Journal of clinical medicine

2022 Volume 11, Issue 15

Abstract: Background: Despite the high COVID-19 morbidity and mortality rates across the world, the reported rates in sub-Saharan Africa (SSA), which has a higher burden of other infectious diseases and overwhelmed healthcare systems, remain relatively low. This ... ...

Abstract	Background: Despite the high COVID-19 morbidity and mortality rates across the world, the reported rates in sub-Saharan Africa (SSA), which has a higher burden of other infectious diseases and overwhelmed healthcare systems, remain relatively low. This study aims to better understand the potential factors that contribute to this phenomenon, especially among cancer patients who are considered as a high-risk group for developing severe COVID-19. Methods: Plasma samples collected during the COVID-19 pandemic from SARS-CoV-2 unvaccinated cancer and potential blood donor populations were analyzed for SARS-CoV-2 (spike and nucleocapsid proteins) antibodies by an immunofluorescence assay. The relationships between SARS-CoV-2 seroprevalences and study variables were determined using a logistic regression analysis. Results: High seroprevalence against the SARS-CoV-2 spike and nucleocapsid proteins were found among the SARS-CoV-2 unvaccinated COVID-19 pandemic populations in SSA. However, the cancer patients demonstrated a lower seroprevalence compared to potential blood donors. There was also an association between mild COVID-19 symptoms with prior tuberculosis vaccination among cancer patients. Conclusion: Cancer patients in SSA tend to have a relatively lower SARS-CoV-2 seroprevalence compared to potential blood donors recruited from the same geographic locations during the COVID-19 pandemic. More study is required to determine its cause and potential impact on SARS-CoV-2 vaccination among cancer patients.
Language	English
Publishing date	2022-07-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm11154428
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Article ; Online: Lack of CD8

Lidenge, Salum J / Tso, For Yue / Ngalamika, Owen / Kolape, Jaydeep / Ngowi, John R / Mwaiselage, Julius / Wood, Charles / West, John T

Oncotarget

2020 Volume 11, Issue 17, Page(s) 1556–1572

Abstract: Despite the close association between Kaposi's sarcoma (KS) and immune dysfunction, it remains unclear whether tumor infiltrating immune cells (TIIC), by their absence, presence, or dysfunction, are mechanistically correlated with KS pathogenesis. ... ...

Abstract	Despite the close association between Kaposi's sarcoma (KS) and immune dysfunction, it remains unclear whether tumor infiltrating immune cells (TIIC), by their absence, presence, or dysfunction, are mechanistically correlated with KS pathogenesis. Therefore, their potential capacity to serve as prognostic biomarkers of KS disease progression or control is unclear. Because epidemic-KS (EpKS) occurs with HIV-1 co-infection, it is particularly important to compare TIIC between EpKS and HIV-negative African endemic-KS (EnKS) to dissect the roles of HIV-1 and Kaposi Sarcoma-associated herpesvirus (KSHV) in KS pathogenesis. This cross-sectional study of 13 advanced KS (4 EnKS, 9 EpKS) patients and 3 healthy controls utilized single-color immunohistochemistry and dual-color immunofluorescence assays to characterize and quantify KSHV infected cells in relation to various TIIC in KS biopsies. Analysis of variance (ANOVA) and Mann-Whitney tests were used to assess differences between groups where
Language	English
Publishing date	2020-04-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.27569
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