Correlates of Kaposi sarcoma-associated herpesvirus seroprevalence in Sicily

Correlates of Kaposi sarcoma-associated herpesvirus seroprevalence in Sicily

Detection of Kaposi’s sarcoma-associated herpesvirus (KSHV) DNA in peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus type 1-infected persons is associated with an increased risk of subsequent development of Kaposi’s sarcoma (13, 15) and with Kaposi’s sarcoma clinical stage (3, 10). Kaposi’s sarcoma-associated herpesvirus (KSHV) proteins are known to subvert autophagic pathways, but the link to Kaposi’s sarcoma pathogenesis is unclear. These eradication programs have generated a currently unmet demand for affordable and sensitive tests that can detect SHV-1 infection, yet distinguish between infected and vaccinated pigs. A dramatic increase in PHV-1 specific antibody, involving the majority of hospitalized pups, was observed during a 4-week period in May. During the identification of CD147 controlled downstream genes by microarray analysis, we found that the expression of HO-1 is significantly elevated in both CD147-overexpressing and KSHV-infected HUVEC cells when compared to control cells. Many viruses spread by infecting nerve terminals and traveling from neuron to neuron in the vertebrate nervous system. These results showed that infection can occur in the absence of obvious disease and that seroconversion may be associated with clinical recovery.

In such models, seroprevalence was higher with exposure to one plant (Hieracium, odds ratio≥2.8), but it was lower with three others (Acanthus mollis, Taraxacum officinalis, and Trigonella foenum-graecum) and with cumulative exposure to all 20 plants (Ptrend=0.03). It is concluded that trypsin treatment might effectively prevent infection of recipients if individual, Day 7, exposed embryos were transferred into the uterus. KSHV seroprevalence appears to be increased by contact with soil and to vary with certain plants. Corroboration and investigation of possible effects of soil and plant constituents on KSHV regulation and immune responses are needed. At least three theories have emerged for how ecologic and environmental exposures could affect KSHV seroprevalence. The simplest is the use of KHSV-infected saliva for hygiene, particularly in water-shortage regions4 or for soothing insect bites.14 The second is the alteration of cellular immunity, as induced by insect bites or particularly by parasites,9 that may increase susceptible target cells, hamper effective responses, or increase KSHV shedding in close contacts. The third is the induction of KSHV lytic replication by exposure to phorbol esters or other constituents of plants or soil, which would increase shedding by contacts.15,16 Exposure to plant or soil constituents could also increase KSHV antigen expression to a critical threshold, resulting in antibody seroconversion among people who are KSHV-infected but seronegative in current assays.

Correlates of Kaposi sarcoma-associated herpesvirus seroprevalence in Sicily
Herein, we sought to identify risk factors for KSHV seropositivity in a population-based study that encompassed the elderly population of Sicily. We focused on socio-demographics, childhood crowding, occupational contact with plants or soil, contact with specific plant species, and various exposures to water. Detailed methods for the parent case-control study of classic KS conducted in Sicily during 2002–2006 have been published.17 Briefly, population-based controls, aged 30–99 years were selected from the National Health System Patients Roster using stratified two-stage cluster sampling. The 4044 primary care physicians were stratified by community size, then randomly selected with the probability proportional to the number of patients on the physician’s roster. Up to 12 controls, frequency matched to KS cases by sex and age in 5-year strata, were selected from each of the 450 selected physicians. Institutional review board approval was obtained from the U.S. National Cancer Institute, local institutions in eastern (Ragusa) and western (Palermo) Sicily, and the coordinating center (RTI International).

Following signed informed consent, recruited participants provided a blood sample and responses to a standardized questionnaire. Demographic variables included age, sex, and education level, as well as the community of residence at birth, during childhood to age 12, during the 10 years before enrollment, and at the time of interview. In addition, participants were asked about childhood crowding and family size, source of drinking water, frequency of bathing and showering, occupational contact with open water, contact with plants or soil, and contact with 20 specific plant species. These 20 plants (listed in , including footnote) were selected on the advice of local botanists based on the prevalence and likelihood of contact in Sicily, known dermal uses or toxicities, or genetic relatedness to plants reported to induce KSHV lytic replication.15,16 To optimize the accuracy of recall, the participant was shown color photographs for each of the 20 plants during the interview. From the Sicilian population of 3.2 million people aged 30–99 years, 4692 controls were selected. Of these, 1232 were enrolled. Major reasons for non-enrollment included termination of recruitment for lack of funds (1268), physician reasons (refused: 510; deceased: 32; closed practice: 48), and patient reasons (refused: 459; not located: 436; too ill: 289; and deceased: 404).

Fourteen failed to meet eligibility. Plasma aliquots of EDTA anti-coagulated blood were tested for KSHV antibodies using four assays: an immunofluorescence assay (IFA) to the latent nuclear antigen (LANA), an IFA to KSHV lytic antigens, and enzyme-linked immunosorbent assays (ELISAs) against the KSHV gene products K8.1 and open reading frame 73 (orf73). Laboratory methods for the assays have been described.18 Briefly, the IFAs were performed with a 1:120dilution of plasma using the BCBL-1 cell line with (lytic) and without (LANA) inductionby phorbol 12-tetradecanoate 13-acetate (TPA). ELISAs with recombinant K8.1 and orf73 proteins were performed with 1:20 and 1:100 dilutions of plasma, respectively. Participants were considered positive if they had a positive LANA and/or an optical density reading (OD) >1.2 on the K8.1 ELISA. Spira, L. This algorithm is a modification of one with an estimated sensitivity of 80%–90% and an estimated specificity of 90%–100%.18 Participants who did not meet the definition of negative or positive (e.g., reactive by lytic IFA or orf73 ELISA but not by LANA or K8.1 ELISA) were classified as sero-indeterminate and included only in sensitivity analyses.

To adjust for the multi-stage sampling of the participants, base weights were calculated as the product of the reciprocal of the selection probabilities at each stage of sampling.17 Non-response adjusted weights were then calculated as the product of these base weights and cross-classified categories of age, region (eastern/western Sicily), and gender. These non-response adjusted weights were further adjusted by using post-stratification to constrain the weights to reflect the population totals by age, gender and six zones (three community sizes × 2 regions). Moreover, a study from Japan found HSV in almost a quarter of the samples from men attending a fertility clinic. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) in toluene was purchased from Supelco (St. 1B). Eisenberg, G.

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