Herpes simplex virus-infected squamous cell carcinoma: a case report

Background Herpes simplex virus (HSV)-1 is a highly prevalent, non-oncogenic virus that has higher morbidity in immunocompromised hosts. Its most common clinical manifestation is superficial ulceration of the integument or mucus membranes. Case presentation A 65-year-old woman with a history of acute myelogenous leukemia treated with allogenic peripheral blood stem cell transplant presented for resection of an ulcerated buccal squamous cell carcinoma. We report a case of HSV-1-infected malignant cells discovered on histopathological examination of the carcinoma specimen ultimately treated with valacyclovir. Conclusions HSV-1 is not considered an oncogenic virus itself but may increase risk of malignant progression. Cancer cells are vulnerable to superimposed viral infections, including HSV-1, which likely led to the findings in this case.

Evolutionary Comparisons of Chelonid Alphaherpesvirus 5 (ChHV5) Genomes from Fibropapillomatosis-Afflicted Green (Chelonia mydas), Olive Ridley (Lepidochelys olivacea) and Kemp’s Ridley (Lepidochelys kempii) Sea Turtles

The spreading global sea turtle fibropapillomatosis (FP) epizootic is threatening some of Earth’s ancient reptiles, adding to the plethora of threats faced by these keystone species. Understanding this neoplastic disease and its likely aetiological pathogen, chelonid alphaherpesvirus 5 (ChHV5), is crucial to understand how the disease impacts sea turtle populations and species and the future trajectory of disease incidence. We generated 20 ChHV5 genomes, from three sea turtle species, to better understand the viral variant diversity and gene evolution of this oncogenic virus. We revealed previously underappreciated genetic diversity within this virus (with an average of 2035 single nucleotide polymorphisms (SNPs), 1.54% of the ChHV5 genome) and identified genes under the strongest evolutionary pressure. Furthermore, we investigated the phylogeny of ChHV5 at both genome and gene level, confirming the propensity of the virus to be interspecific, with related variants able to infect multiple sea turtle species. Finally, we revealed unexpected intra-host diversity, with up to 0.15% of the viral genome varying between ChHV5 genomes isolated from different tumours concurrently arising within the same individual. These findings offer important insights into ChHV5 biology and provide genomic resources for this oncogenic virus.

Evolutionary Genomic Comparisons of Chelonid Herpesvirus 5 (chhv5) From Fibropapillomatosis-Afflicted Green (Chelonia Mydas), Olive Ridley (Lepidochelys Olivacea), And Kemp’s Ridley (Lepidochelys Kempii) Sea Turtles.

The spreading global sea turtle fibropapillomatosis (FP) epizootic is threatening some of Earth’s ancient reptiles, adding to the plethora of threats faced by these keystone species. Understanding this neoplastic disease, and its likely aetiological pathogen, chelonid alphaherpesvirus 5 (ChHV5), is crucial to understand how the disease impacts sea turtle populations and species and the future trajectory of disease incidence. We generated 20 ChHV5 genomes, from three sea turtle species, to better understand the viral variant diversity and gene evolution of this oncogenic virus. We revealed previously underappreciated genetic diversity within this virus (with an average of 2,035 single nucleotide polymorphisms [SNPs], 1.54% of the ChHV5 genome) and identified genes under the strongest evolutionary pressure. Furthermore, we investigated the phylogeny of ChHV5 at both genome and gene level, confirming the propensity of the virus to be interspecific with related variants able to infect multiple sea turtle species. Finally, we revealed unexpected intra-host diversity, with up to 0.15% of the viral genome varying between ChHV5 genomes isolated from different tumours concurrently arising within the same individual. These findings offer important insights into ChHV5 biology and provide genomic resources for this oncogenic virus.

Kaposi’s sarcoma-associated herpesvirus (KSHV) processivity factor, ORF59, binds to canonical and linker histones, and carboxy-terminus is dispensable for viral DNA synthesis

Kaposi’s sarcoma-associated herpesvirus (KSHV) is a human oncogenic virus and the causative agent of Kaposi’s sarcoma, multicentric Castleman’s disease, and primary effusion lymphoma. During lytic reactivation there is a temporal cascade of viral gene expression that results in the production of new virions. One of the viral factors that is expressed during reactivation is open reading frame (ORF) 59, the viral DNA polymerase processivity factor. ORF59 plays an essential role for DNA synthesis and is required for the nuclear localization of the viral DNA polymerase (ORF9) to the origin of lytic replication (oriLyt). In addition to its functions in viral DNA synthesis, ORF59 has been shown to interact with chromatin complexes including histones and cellular methyltransferases. In this study, a series of KSHV BACmids containing 50 aa deletions within ORF59 were generated to determine the interaction domains between ORF59 and histones, as well as to assess the effects on replication fitness as a result of these interactions. These studies show that in the context of infection ORF59 51-100 and 151-200 amino acids (aa) are required for interaction with histones, and ORF59 301-396 aa are not required for DNA synthesis. Since full length ORF59 is known to localize to the nucleus, we performed immunofluorescent assay (IFA) with the ORF59 deletion mutants and showed that all deletions are localized to the nucleus, this includes the ORF59 deletion without the previously identified nuclear localization signal (NLS). These studies further characterize ORF59 and demonstrate its essential role during lytic replication. IMPORTANCE. KSHV is an oncogenic virus and the causative agent of potentially fatal malignancies. Lytic replication of KSHV is an essential part of the viral lifecycle, allowing for virus dissemination within the infected host and shedding to infect naïve hosts. Viral DNA synthesis is a critical step in the production of new infectious virions. One of the proteins that is vital to this process is ORF59, the viral encoded polymerase processivity factor. Previous work has demonstrated that the function of ORF59 is closely connected to its association with other viral and cellular factors. The studies presented here extend that work to include the interaction between ORF59 and histones. This interaction offers an additional level of regulation of the chromatinized viral genome, ultimately influencing DNA synthesis and transcription dynamics.

Polyamine biosynthesis and eIF5A hypusination are modulated by the DNA tumor virus KSHV and promote KSHV viral infection

Polyamines are critical metabolites involved in various cellular processes and often dysregulated in cancers. Kaposi’s sarcoma associated Herpesvirus (KSHV) is a defined oncogenic virus belonging to the sub-family of human gamma-herpesviruses. KSHV infection leads to the profound alteration of host metabolic landscape to favor the development of KSHV-associated malignancies. In our studies, we identified that polyamine biosynthesis and eIF5A hypusination are dynamically regulated by KSHV infection likely through the modulation of key enzymes of these pathways, such as ODC1, and that in return these metabolic pathways are required for both KSHV lytic switch from latency and de novo infection. The further analysis unraveled that translation of critical KSHV latent and lytic proteins (LANA, RTA) depends on eIF5A hypusination. We also demonstrated that KSHV infection can be efficiently and specifically suppressed by using inhibitors targeting either polyamine biosynthesis or eIF5A hypusination. Above all, our results illustrated that the dynamic and profound interaction of a DNA tumor virus (KSHV) with host polyamine biosynthesis and eIF5A hypusination metabolic pathways promote viral propagation and oncogenesis, which serve as new therapeutic targets to treat KSHV-associated malignancies.

In VivoModels of Oncoproteins Encoded by Kaposi’s Sarcoma-Associated Herpesvirus

ABSTRACTKaposi’s sarcoma-associated herpesvirus (KSHV) is a human oncogenic virus. KSHV utilizes its proteins to modify the cellular environment to promote viral replication and persistence. Some of these proteins are oncogenic, modulating cell proliferation, apoptosis, angiogenesis, genome stability, and immune responses, among other cancer hallmarks. These changes can lead to the development of KSHV-associated malignancies. In this Gem, we focus on animal models of oncogenic KSHV proteins that were developed to enable better understanding of KSHV tumorigenesis.