SUMMARY Aplastic crises in homozygous sickle cell disease in Jamaica predominantly affect children and occur in epidemics. Of 67 cases in a cohort study of 314 children with homozygous sickle cell disease, 62 were attributable to human parvovirus infection. Affected children were aged 0*5-12.5 years, and the incidence rose to 28% by 10 years. No recurrences were seen. Symptoms and signs on presentation were attributable to the viraemia and acute anaemia. Asymptomatic thrombocytopenia was common. Blood transfusion was given in 54 cases (87%). Thirty eight children (61%) were admitted to hospital, 16 of whom were extremely ill on presentation and one of whom died soon after admission. Twenty four (39%) were managed as outpatients, 16 of whom were transfused. Parvovirus associated aplastic crisis is a self limited condition with excellent prognosis if diagnosed promptly and managed appropriately.The aplastic crisis occurs in a variety of chronic haemolytic conditions.'-4 A temporary stopping of erythropoiesis is followed by a rapid fall in haemoglobin concentration, and death may result from peripheral circulatory failure. Most episodes are associated with human parvovirus infection.3 5-8 Of 67 aplastic crises in a cohort study of sickle cell disease, 62 were attributable to parvovirus infection.
Patients and methods
Kaposi’s sarcoma-associated herpesvirus (KSHV) causes several human cancers, such as Kaposi’s sarcoma (KS) and primary effusion lymphoma (PEL). Current treatment options for KSHV infection and virus associated diseases are sometimes ineffective, therefore, more effectively antiviral agents are urgently needed. As a herpesvirus, lytic replication is critical for KSHV pathogenesis and oncogenesis. In this study, we have established a high-throughput screening assay by using an inducible KSHV+ cell-line, iSLK.219. After screening a compound library that consisted of 1280 Food and Drug Administration (FDA)-approved drugs, 15 hit compounds that effectively inhibited KSHV virion production were identified, most of which have never been reported with anti-KSHV activities. Interestingly, 3 of these drugs target histamine receptors or signaling. Our data further confirmed that antagonists targeting different histamine receptors (HxRs) displayed excellent inhibitory effects on KSHV lytic replication from induced iSLK.219 or BCBL-1 cells. In contrast, histamine and specific agonists of HxRs promoted viral lytic replication from induced iSLK.219 or KSHV-infected primary cells. Mechanistic studies indicated that downstream MAPK and PI3K/Akt signaling pathways were required for histamine/receptors mediated promotion of KSHV lytic replication. Direct knockdown of HxRs in iSLK.219 cells effectively blocked viral lytic gene expression during induction. Using samples from a cohort of HIV+ patients, we found that the KSHV+ group has much higher levels of histamine in their plasma and saliva than the KSHV- group. Taken together, our data have identified new anti-KSHV agents and provided novel insights into the molecular bases of host factors that contribute to lytic replication and reactivation of this oncogenic herpesvirus.
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