[PubMed] [Google Scholar] 44

[PubMed] [Google Scholar] 44. but find no evidence of the proposed phenotypic switch in either the subclass of parvovirus B19-specific antibody or the pattern of cytokine production by antigen-specific T cells. The dominating subclass of specific antibody recognized from both children and adults was immunoglobulin G1. No evidence was found for interleukin 4 (IL-4) or IL-5 production by isolated lymphocytes from children or adults. In contrast, lymphocytes from convalescent adults produced a typical type 1 response associated with high levels of IL-2 and gamma interferon (IFN-). However, we observed a significant ( 0.001) deficit in the production of IFN- in response to VP1 or VP2 from lymphocytes isolated from children. Taken collectively, these results imply that future parvovirus B19 vaccines designed for children will require the use of conformationally maintained capsid proteins incorporating Th1 traveling adjuvants. Furthermore, these data suggest novel mechanisms whereby parvovirus B19 illness may contribute to rheumatoid arthritis and unsuccessful pregnancy. Human being parvovirus B19 (B19V) causes the common childhood illness JNJ-7706621 known as fifth disease or erythema infectiosum. While the symptoms are generally slight, there are a variety of conditions under which illness has more severe results. In the immunocompromised or individuals with underlying hemolytic disorders, such as sickle-cell disease and hereditary spherocytosis, illness with B19V can result in an acute aplastic problems or in chronic anemia (39, 53). During pregnancy, the virus can be transmitted transplacentally from an infected mother to the fetus and may cause spontaneous abortion or fetal anemia JNJ-7706621 (9). Direct illness of the JNJ-7706621 fetus can result in nonimmune hydrops fetalis. B19V has also been linked to arthritis in adults and children (41). It has been estimated that 60% of ladies with symptomatic disease manifest arthropathy (53). The symptoms generally subside within 3 weeks, but about 20% of affected ladies suffer a prolonged or repeating arthropathy. At present there is no effective vaccine available either for ladies of child-bearing age or for the general population. B19V is definitely a small, nonenveloped, single-stranded DNA computer virus classified as an erythrovirus. The computer virus replicates in human being erythroid progenitor cells of the bone marrow and blood, inhibiting erythropoiesis (54). Illness with B19V is definitely common, and upwards of 60 to 70% of the population is definitely seropositive by adulthood (8). Transmission most commonly happens by personal contact via aerosol or respiratory secretions; however, JNJ-7706621 contaminated blood products may also be a source of iatrogenic transmission. The B19V capsid consists of an 83-kDa small structural protein, VP1, and a 53-kDa major structural protein, VP2. VP2 makes up about 95% of the total capsid, with VP1 making up the remainder (38). The sequences of the two proteins are colinear, with VP2 becoming identical to the carboxyl terminus of VP1; however, VP1 contains an additional 227 amino acids unique to the amino-terminal end. Although little is known about the protecting immune response against B19V in humans, specific antiviral antibody is considered the major mechanism of protection. This is based on the circumstantial evidence that high-dose immunoglobulin therapy is sometimes beneficial for infected individuals (23, 43). This treatment does not work in all instances, and no data is definitely available on the actual protecting level of B19V immunoglobulin G (IgG), although levels greater than 6 IU are thought to be protecting (44). It has been previously demonstrated that a time-dependent switch in antibody response happens against viral capsid proteins by an unfamiliar mechanism (47). It is characterized by a loss of antibody specificity against linear viral epitopes of VP1 and VP2 and also by a proposed antibody subclass switch from IgG3 to IgG4. It has been speculated that this switch is definitely caused by an underlying alteration in the type of CD4+ T-cell response; however, there has been very little examination of this response in humans (16, 51). It is approved that in response to FLT3 antigen, T helper (Th) cells secrete cytokines, which are involved in regulatory functions or can mediate direct activity against invading viruses. The current paradigm is definitely that Th cells can be subdivided into at least three populations according to the pattern of cytokines secreted on activation. Th1 cells secrete interleukin 2 (IL-2), gamma interferon (IFN-), and tumor necrosis element beta, Th2 cells secrete IL-4 and IL-5 (34), and the recently explained regulatory subset (Tr1) generates IL-10 (1, 13, 33, 40). The Th cell subset classification also correlates with a functional JNJ-7706621 dichotomy. Th1 cells are the principal effectors of proinflammatory reactions, delayed-type hypersensitivity, and cell-mediated immunity against intracellular pathogens. The.