In addition, there is evidence that increased incidence of retinitis in patients with AIDS is associated with the gB genotype (40)
In addition, there is evidence that increased incidence of retinitis in patients with AIDS is associated with the gB genotype (40). Although the underlying mechanisms for the different clinical outcome of HCMV infections are unexplained, strain-specific immune responses might play an important role in clinical situations where reinfections occur and where the de novo immune response against viral antigens is impaired as, for example, in transplant patients or in individuals infected with human immunodeficiency virus. the neutralizing antibodies and that neutralization is largely independent of the concentration of virus. Analysis with transplant patients revealed that during primary infection strain-specific and strain-common antibodies are produced asynchronously. Thus, our data demonstrate that the induction of strain-specific neutralizing antibodies is a common event during infection with HCMV and that it might have important implications for the course of the infection and the development of anti-HCMV vaccines. Human cytomegalovirus (HCMV) remains a significant pathogen in individuals with an immature or compromised immune system. In contrast, infection of immunocompetent persons has had limited consequences in the vast majority of cases, indicating the importance of a functional immune response in the control of HCMV infections (23). Although the immunological effector functions which control HCMV are incompletely understood, it must be assumed that the humoral immune response represents an important defense mechanism against HCMV. It is well established that seroimmunity to HCMV prior to conception provides substantial protection against symptomatic infection of the newborn (19, 44). In a recent vaccination study it was also demonstrated that protection from reinfection is correlated with the titers of neutralizing antibodies but not of T cells (2). In transplant recipients the absence of viral DNA in the blood is associated with high levels of neutralizing antibodies 360A iodide (39). Moreover, passive transfer of antibodies seems to have a beneficial effect on the clinical outcome of infection (41, 49). In the murine cytomegalovirus model, protection from a lethal challenge can be achieved by using monoclonal antibodies (MAbs) or immune sera directed against glycoproteins B (gB) and H (gH), respectively (18, 34). In addition, antibodies are Rabbit polyclonal to CD20.CD20 is a leukocyte surface antigen consisting of four transmembrane regions and cytoplasmic N- and C-termini. The cytoplasmic domain of CD20 contains multiple phosphorylation sites,leading to additional isoforms. CD20 is expressed primarily on B cells but has also been detected onboth normal and neoplastic T cells (2). CD20 functions as a calcium-permeable cation channel, andit is known to accelerate the G0 to G1 progression induced by IGF-1 (3). CD20 is activated by theIGF-1 receptor via the alpha subunits of the heterotrimeric G proteins (4). Activation of CD20significantly increases DNA synthesis and is thought to involve basic helix-loop-helix leucinezipper transcription factors (5,6) the limiting factor for the prevention of virus dissemination (25). Collectively, these findings point to a major role of antibodies in limiting the consequences of a HCMV infection. Although no two HCMV isolates are identical with respect to the restriction endonuclease patterns of the entire genomes, strain variations have been considered to be of little consequence for the host (12, 21). However, in recent years several studies have suggested that strain differences might contribute to the clinical course of the infection. For example, in kidney transplant recipients reinfection with a genetically different donor virus is associated with a higher risk of developing severe HCMV disease than of reactivation of the endogenous virus (22). Likewise, survival rates of bone marrow transplant recipients with HCMV infection have been linked to specific genotypes of the envelope gB (gpUL55) (20). In addition, there is evidence that increased incidence of retinitis in patients with AIDS is associated with the gB genotype (40). Although the underlying mechanisms for the different clinical outcome of HCMV infections are unexplained, strain-specific immune responses might play an important role in clinical situations where reinfections occur and where the de novo immune response against viral antigens is impaired as, for example, in transplant patients or in individuals infected 360A iodide with human immunodeficiency virus. In addition, strain-specific immune responses might hamper the development of an effective vaccine. Antibodies against envelope glycoproteins could be particularly important since they have been shown to neutralize virus. Thus far, gB and gH (gpU175) have been identified as dominant targets for the humoral immune response, and 360A iodide immunoglobulins reacting with these antigens have been characterized in some detail (for a review, see reference 10). Extensive strain-specific virus neutralization has been observed in the vast majority of studies that have employed against gB and gH in the neutralization of different clinical HCMV isolates, and some of the B-cell epitopes involved have been characterized (6, 32, 35, 45). For polyclonal 360A iodide sera, the situation is.