Mutual detection of Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus in blood and saliva of Cameroonians with and without Kaposi's sarcoma.

Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are prevalent in sub-Saharan Africa, together with HIV; the consequent burden of disease is grave. The cofactors driving transmission of the two viruses and pathogenesis of associated malignancies are not well understood. We measured KSHV and EBV DNA in whole blood and saliva as well as serum antibodies levels in 175 Cameroonians with Kaposi's sarcoma and 1,002 age- and sex-matched controls with and without HIV. KSHV seroprevalence was very high (81%) in controls, while EBV seroprevalence was 100% overall. KSHV DNA was detectable in the blood of 36-46% of cases and 6-12% of controls; EBV DNA was detected in most participants (72-89%). In saliva, more cases (50-58%) than controls (25-28%) shed KSHV, regardless of HIV infection. EBV shedding was common (75-100%); more HIV+ than HIV- controls shed EBV. Cases had higher KSHV and EBV VL in blood and saliva then controls, only among HIV+ participants. KSHV and EBV VL were also higher in HIV+ than in HIV- controls. Cases (but not controls) were more likely to have detectable KSHV in blood if they also had EBV, whereas shedding of each virus in saliva was independent. While EBV VL in saliva and blood were modestly correlated, no correlation existed for KSHV. Numerous factors, several related to parasitic coinfections, were associated with detection of either virus or with VL. These findings may help better understand the interplay between the two gammaherpesviruses and generally among copathogens contributing to cancer burden in sub-Saharan Africa.

Longitudinal associations among peer victimization and physical and mental health problems.

OBJECTIVE: This study examined how chronic experiences of peer victimization throughout childhood relate to mental and physical health outcomes in adolescence. METHODS: Children were tested in a laboratory playroom at the age of 5 years. They completed questionnaires at time 2, between the ages of 10 and 18 years, and a telephone interview at time 3, between the ages of 12 and 20 years. A total of 70 youth participated at all three time periods. Chronic victims were defined as having high levels of peer victimization at all three time points. RESULTS: Youth who were chronically victimized reported experiencing significantly more mental and physical health problems than youth categorized as desisters or nonvictims. Also, for girls only, chronic victims reported more specific health problems (headaches, sleep problems) than did nonchronic victims. CONCLUSIONS: The present findings may assist health professionals in assessing and treating physical and mental health problems that appear to be related to peer victimization.

T-cell responses to KSHV infection: a systematic approach.

Prior studies of T-cell responses to KSHV have included relatively few participants and focused on relatively few KSHV antigens. To provide a more comprehensive analysis, we investigated T-cell responses to the whole KSHV proteome using IFN-γ ELISpot. Using ∼7,500 overlapping 15mer peptides we generated one to three peptide pools for each of the 82 KSHV ORFs. IFN-γ ELISpot analysis of PBMCs from 19 patients with a history of KSHV-associated disease and 24 healthy donors (11 KSHV seropositive) detected widely varied responses. Fifty six of the 82 ORFs were recognized by at least one individual but there was little overlap between participants. Responses to at least one ORF pool were observed in all 19 patients and in 7 seropositive donors. Four seropositive donors and 10 seronegative donors had no detectable responses while 3 seronegative donors had weak responses to one ORF. Patients recognised more ORFs than the donors (p=0.04) but the response intensity (spot forming units: SFU per million cells) was similar in the two groups. In four of the responding donors, individual peptides eliciting the predominant responses were identified: three donors responded to only one peptide per ORF, while one recognized five. Using intracellular cytokine staining in four participant samples, we detected peptide-induced IFN-γ, MIP1-ß, and TNF-α as well as CD107a degranulation, consistent with multifunctional effector responses in CD8+ and CD4+ T cells. Sequence analysis of TCRs present in peptide specific T-cell clones generated from two participants showed both mono- and multi-clonotypic responses. Finally, we molecularly cloned the KSHV specific TCRs and incorporated the sequences into retroviral vectors to transfer the specificities to fresh donor cells for additional studies. This study suggests that KSHV infected individuals respond to diverse KSHV antigens, consistent with a lack of shared immunodominance and establishes useful tools to facilitate KSHV immunology studies.

Marine lipid fraction PCSO-524 (lyprinol/omega XL) of the New Zealand green lipped mussel attenuates hyperpnea-induced bronchoconstriction in asthma.

PURPOSE: Evaluate the effect of the marine lipid fraction of the New Zealand green-lipped mussel (Perna canaliculus) PCSO-524 (Lyprinol/Omega XL), rich in omega-3 fatty acids, on airway inflammation and the bronchoconstrictor response to eucapnic voluntary hyperpnea (EVH) in asthmatics. METHODS: Twenty asthmatic subjects, with documented HIB, participated in a placebo controlled double-blind randomized crossover trial. Subjects entered the study on their usual diet and were then placed on 3 weeks of PCSO-524 or placebo supplementation, followed by a 2 week washout period, before crossing over to the alternative diet. Pre- and post-eucapnic voluntary hyperpnea (EVH) pulmonary function, fraction of exhaled nitric oxide (FENO), asthma symptom scores, medication use, exhaled breath condensate (EBC) pH, cysteinyl leukotrienes (cyst-LT), 8-isoprostane and urinary 9α, 11ß-prostaglandin (PG)F2 and Clara (CC16) protein concentrations were assessed at the beginning of the trial and at the end of each treatment period. RESULTS: The PCSO-524 diet significantly reduced (p < 0.05) the maximum fall in post-EVH FEV1 (-8.4 ± 3.2%) compared to usual (-19.3 ± 5.4%) and placebo diet (-22.5 ± 13.7%). Pre- and post- EVH EBC cyst-LT and 8-isoprostane, and urinary 9α, 11ß-PGF2 and CC16 concentrations were significantly reduced (p < 0.05) on the PCSO-524 diet compared to the usual and placebo diet. EBC pH and asthma symptom scores were significantly improved (p < 0.05) and rescue medication use significantly reduced (p < 0.05) on the PCSO-524 diet compared to the usual and placebo diet. CONCLUSION: PCSO-524 (Lyprinol)/Omega XL) may have beneficial effects in HIB and asthma by serving as a pro-resolving agonist and/or inflammatory antagonist.