Human Herpes Virus 8 in HIV-1 infected individuals receiving cancer chemotherapy and stem cell transplantation

Abstract

BackgroundHuman Herpes Virus 8 (HHV8) can cause Kaposi’s Sarcoma (KS) in immunosuppressed individuals. However, little is known about the association between chemotherapy or hematopoietic stem cell transplantation (HSCT), circulating HHV8 DNA levels, and clinical KS in HIV-1-infected individuals with various malignancies. Therefore, we examined the associations between various malignancies, systemic cancer chemotherapy, T cell phenotypes, and circulating HHV8 DNA in 29 HIV-1-infected participants with concomitant KS or other cancer diagnoses.MethodsWe quantified HHV8 plasma viral loads and cell-associated HHV8 DNA and determined the relationship between circulating HHV8 DNA and lymphocyte counts, and markers of early and late lymphocyte activation, proliferation and exhaustion.ResultsThere were no significant differences in plasma HHV8 DNA levels between baseline and post-chemotherapy time points or with the presence or absence of clinical KS. However, in two participants circulating HHV8 DNA increased following treatment for KS or HSCT for lymphoma,. We observed an approximately 2-log10 reduction in plasma HHV8 DNA in an individual with KS and multicentric Castleman disease following rituximab monotherapy. Although individuals with clinical KS had lower mean CD4+ T cell counts and percentages as expected, there were no significant associations with these factors and plasma HHV8 levels. We identified increased proportions of CD8+ and CD4+ T cells expressing CD69 (P = 0.01 & P = 0.04 respectively), and increased CD57 expression on CD4+ T cells (P = 0.003) in participants with detectable HHV8.ConclusionThese results suggest there is a complex relationship between circulating HHV8 DNA and tissue-based disease in HIV-1 and HHV8 co-infected individuals with various malignancies.

Use of viral motif mimicry improves the proteome-wide discovery of human linear motifs

“…Accordingly, Roscovitine can be potentially repurposed as pharmacological therapy for HPV 11 infections. Moreover, several other drugs that we identified ( Figure 7 ) already have indications in ChEMBL or evidence for reducing the relevant viral infection, such as Sirolimus and Everolimus for Influenza A infection (Alsuwaidi et al, 2017; Murray et al, 2012), Vorinostat and Cytarabine for human herpesvirus type-8 (hhv8) (Hogan et al, 2018; Jc et al, 2020), and Erlotinib, Vatalanib, and Dasatinib for Hepatitis C (HCV) (Lupberger et al, 2011; Elsebai et al, 2016).…”

“…In a search for drug repurposing candidates, we also identified drugs that target domain-carrying properties that we predicted to be relevant both for the viral infection and associated ClinVar disease. While only 13 drugs targeting 5 of our proteins were retrieved, several of them already had indications for the relevant viral infection in addition to the disease used to extract the drugs from the database (Alsuwaidi et al, 2017; Elsebai et al, 2016; Hogan et al, 2018; Jc et al, 2020; Lupberger et al, 2011; Murray et al, 2012). This suggests that our collection of paired viral-human motifs could be a good starting point for identifying key nodes to target in the pathogenesis of both the disease associated with the motif mutations and the viral infections.…”

Use of viral motif mimicry improves the proteome-wide discovery of human linear motifs

“…In a search for drug repurposing candidates, we also identified drugs that target domain-carrying proteins that we predicted to be relevant both for the viral infection and associated ClinVar disease. While only 13 drugs targeting five of our proteins were retrieved, several of them already had indications for the relevant viral infection in addition to the disease used to extract the drugs from the database (Alsuwaidi et al, 2017;Elsebai et al, 2016;Hogan et al, 2018;Ramos et al, 2020;Lupberger et al, 2011;Murray et al, 2012). This suggests that our collection of paired viral-human motifs could be a good starting point for identifying Figure 5.…”

“…Accordingly, roscovitine can potentially be repurposed as pharmacological therapy for HPV11 infections. Moreover, several other drugs that we identified (Figure 6) already have indications in ChEMBL or evidence for reducing the relevant viral infection, such as sirolimus and everolimus for influenza A infection (Alsuwaidi et al, 2017;Murray et al, 2012), vorinostat and cytarabine for human herpesvirus type 8 (hhv8) (Hogan et al, 2018;Ramos et al, 2020), and erlotinib, vatalanib, and dasatinib for hepatitis C virus (HCV) (Elsebai et al, 2016;Lupberger et al, 2011).…”

Case Report: Metagenomic Next-Generation Sequencing Can Contribute to the Diagnosis and Treatment of Disseminated Visceral Kaposi Sarcoma Following Allogeneic Haematopoietic Stem Cell Transplantation

“…In most reported cases, the patient died in less than 1 year during the follow-up period. However, little is known about the potential association of lymphocyte number with circulating HHV-8 DNA levels during different periods after HSCT ( 8 , 9 ). Trials in this field have not been feasible due to the rarity of disease.…”