ABSTRACT
Kaposi sarcoma (KS)-associated herpesvirus (KSHV/HHV-8) was first sequenced from the body cavity (BC) lymphoma cell line, BC-1, in 1996. Few other KSHV genomes have been reported. Our knowledge of sequence variation for this virus remains spotty. This study reports additional genomes from historical US patient samples and from African KS biopsies. It describes an assay that spans regions of the virus that cannot be covered by short read sequencing. These include the terminal repeats, the LANA repeats, and the origins of replication. A phylogenetic analysis, based on 107 genomes, identified three distinct clades; one containing isolates from USA/Europe/Japan collected in the 1990s and two of Sub-Saharan Africa isolates collected since 2010. This analysis indicates that the KSHV strains circulating today differ from the isolates collected at the height of the AIDS epidemic. This analysis helps experimental designs and potential vaccine studies.
Subject(s)
Genome, Viral , Genomics , Genotype , Herpesviridae Infections/virology , Herpesvirus 8, Human/classification , Herpesvirus 8, Human/genetics , Sarcoma, Kaposi/virology , Adult , Cell Line , Female , Gene Expression Regulation, Viral , Genomics/methods , Herpesviridae Infections/diagnosis , Herpesvirus 8, Human/isolation & purification , High-Throughput Nucleotide Sequencing , Humans , Male , Middle Aged , Phenotype , Phylogeny , Recombination, GeneticABSTRACT
This study was conducted to determine the prevalence of respiratory viral infections (RVI) in persons living with HIV (PLH) admitted with a respiratory complaint using real-time reverse transcription polymerase chain reaction and primer-independent next-generation sequencing (NGS). Of 82 subjects, respiratory viruses were the most common pathogen identified in 27 (33%), followed by fungus and bacteria in 8 (10%) and 4 (5%) subjects, respectively. Among subjects with RVI, 11 (41%) required ICU admission and 16 (59%) required mechanical ventilation. The proportion of respiratory viruses identified, and the associated complicated hospital course highlights the significant role that RVIs play in the lung health of PLH.
Subject(s)
HIV Infections/epidemiology , HIV Infections/virology , High-Throughput Nucleotide Sequencing , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology , Viruses/genetics , Cost of Illness , Female , HIV/genetics , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Pneumonia, Viral/epidemiology , Prevalence , Prospective Studies , Respiratory Tract Infections/complications , Tertiary Care Centers/statistics & numerical data , Viruses/classification , Viruses/isolation & purification , Viruses/pathogenicityABSTRACT
Extracellular signaling is a mechanism that higher eukaryotes have evolved to facilitate organismal homeostasis. Recent years have seen an emerging interest in the role of secreted microvesicles, termed extracellular vesicles (EV) or exosomes in this signaling network. EV contents can be modified by the cell in response to stimuli, allowing them to relay information to neighboring cells, influencing their physiology. Here we show that the tumor virus Kaposi's Sarcoma-associated herpesvirus (KSHV) hijacks this signaling pathway to induce cell proliferation, migration, and transcriptome reprogramming in cells not infected with the virus. KSHV-EV activates the canonical MEK/ERK pathway, while not alerting innate immune regulators, allowing the virus to exert these changes without cellular pathogen recognition. Collectively, we propose that KSHV establishes a niche favorable for viral spread and cell transformation through cell-derived vesicles, all while avoiding detection.
Subject(s)
Cellular Reprogramming/physiology , Extracellular Vesicles/physiology , Herpesvirus 8, Human/metabolism , Cell Movement , Cell Proliferation , Cell Transformation, Neoplastic/metabolism , Cellular Reprogramming/genetics , Endothelial Cells/physiology , Herpesvirus 8, Human/genetics , Host-Pathogen Interactions , Human Umbilical Vein Endothelial Cells , Humans , Lymphoma/genetics , Lymphoma/metabolism , Sarcoma, Kaposi/metabolism , Sarcoma, Kaposi/virology , Signal Transduction , Transcriptome/genetics , Viral Proteins , Virus LatencyABSTRACT
BACKGROUND: Previous reports suggest an association between Bartonella infection and effusions in dogs and human beings. OBJECTIVES: The aims of this study were to determine the prevalence of Bartonella infection in canine effusions and to investigate historic and clinical parameters predictive of Bartonella in dogs with effusions. METHODS: Canine cavitary effusions submitted for analysis and, if available, paired EDTA blood, were screened for Bartonella infection using the Bartonella α-proteobacteria growth medium enrichment culture/PCR diagnostic platform (Bartonella enrichment PCR or ePCR) at Galaxy Diagnostics, Inc. RESULTS: Bartonella henselaeDNA was PCR-amplified and sequenced from 15% (12/80) of sampled dogs. Enrichment culture prior to PCR testing was required for Bartonella detection in 92% (11/12) of cases. Twenty percent (4/20), 13% (8/60), and 0% (0/4) of dogs with pleural, peritoneal, and pericardial effusions, respectively, tested positive. Bartonella henselae was detected most frequently in the fall, and young and middle-aged dogs appeared to be overrepresented. Golden Retrievers and Yorkshire/Silky Terriers each comprised 25% of infected dogs (odds ratio 3.4 for Golden Retrievers). There was a weak association with hemorrhagic effusions. Fifty percent of Bartonella-positive dogs had hemorrhage as a component of their effusion compared to 37% of PCR-negative dogs (odds ratio 1.7). CONCLUSIONS: Viable B henselae organisms occur in pleural and peritoneal effusions of dogs; the clinical relevance of which remains unclear and may represent opportunistic infection. Associations found in this study included seasonal variation, age, breed, and site of effusion.
