Kaposi sarcoma herpesvirus (KSHV/HHV-8) is a B cell tropic human pathogen, which is present in vivo in monotypic immunoglobulin λ (Igλ) light chain but polyclonal B cells. In the current study, we use cell sorting to infect specific B cell lineages from human tonsil specimens in order to examine the immunophenotypic alterations associated with KSHV infection. We describe IL-6 dependent maturation of naïve B lymphocytes in response to KSHV infection and determine that the Igλ monotypic bias of KSHV infection in vivo is due to viral induction of BCR revision. Infection of immunoglobulin κ (Igκ) naïve B cells induces expression of Igλ and isotypic inclusion, with eventual loss of Igκ. We show that this phenotypic shift occurs via re-induction of Rag-mediated V(D)J recombination. These data explain the selective presence of KSHV in Igλ B cells in vivo and provide the first evidence that a human pathogen can manipulate the molecular mechanisms responsible for immunoglobulin diversity.
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http://dx.doi.org/10.1371/journal.ppat.1006967 | DOI Listing |
J Med Virol
January 2025
Microbiology Department, University of Massachusetts, Amherst, Massachusetts, USA.
Kaposi's sarcoma-associated herpesvirus is an oncogenic gammaherpesvirus that plays a major role in several human malignancies, including Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. The complexity of KSHV biology is reflected in the sophisticated regulation of its biphasic life cycle, consisting of a quiescent latent phase and virion-producing lytic replication. KSHV expresses coding and noncoding RNAs, including microRNAs and long noncoding RNAs, which play crucial roles in modulating viral gene expression, immune evasion, and intercellular communication.
View Article and Find Full Text PDFJ Med Virol
January 2025
Department of Pathology, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
An outbreak of the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 pandemic, has resulted in over 7 million confirmed deaths. In addition to severe respiratory and systematic symptoms, several comorbidities increase the risk of fatal outcomes. Therefore, it is essential to investigate the impact of COVID-19 on pre-existing conditions in patients, such as cancer and other infectious diseases.
View Article and Find Full Text PDFAm J Transplant
December 2024
Division of Infectious Diseases and Geographic Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Trop Med Infect Dis
December 2024
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Kaposi sarcoma-associated herpes virus (KSHV), also known as human herpes virus 8 (HHV-8), is the primary etiologic cause of Kaposi sarcoma (KS) and KSHV Inflammatory Cytokine Syndrome (KICS). Patients with KICS demonstrate symptoms of systemic inflammation, high KSHV viral load, elevation of inflammatory markers, and increased mortality. Management requires rapid diagnosis, treatment of underlying HIV, direct treatment of KS, and addressing the hyperimmune response.
View Article and Find Full Text PDFbioRxiv
December 2024
Department of Medical Biology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
Caviid gammaherpesvirus 1 (CaGHV-1), formerly known as the guinea pig herpes-like virus, is an oncogenic gammaherpesvirus with a sequenced genome but an as-yet uncharacterized transcriptome. Using nanopore long-read RNA sequencing, we annotated the CaGHV-1 genome and constructed a detailed transcriptomic atlas. Our findings reveal diverse viral mRNAs and non-coding RNAs, along with mapped promoter elements for each viral gene.
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