Abstract: Human CMV is the predominant infectious cause of congenital birth defects and an opportunistic pathogen in immunosuppressed individuals, including AIDS patients. Most individuals are infected early during their life followed by life-long latent infection. During this latent phase, frequent reactivation and antigen production continue to stimulate the immune system. While the immune response is able to control the virus, it is unable to eradicate it. Moreover, super-infection by different CMV strains has been observed despite a strong immune response. Long-term immune stimulation by CMV has also been implicated in immune senescence and chronic conditions such as atherosclerosis. CMVs are highly species-specific and the relatedness of CMV genomes exactly mirrors the relatedness of their hosts. Thus, each CMV species is highly adapted to its respective host species, but is unable to infect other, even closely related hosts. While fascinating from an evolutionary perspective, this host restriction prevents studying HCMV in experimental animals. Exceptions are severely immunocompromised mice, e.g. SCID mice, or SCID/NOD mice, which might allow partial reconstitution of CMV infection in rodents. More practical however, is to study CMVs in their natural host, e.g. murine, rat or guinea pig CMVs. However, while these small animal models have many advantages, such as the availability of inbred animals as well as lower cost, the limited homology of the viral genomes with HCMV limits the functional analysis of homologous gene products. The closest relative to HCMV is chimpanzee CMV (CCMV), but this is not a practical animal model since chimps are a protected species, extremely expensive and of very limited availability. In contrast, rhesus macaques are a more widely used experimental animal species and, while more distant than CCMV, rhesus CMV (RhCMV) contains most of the HCMV gene families thus allowing the study of their role in acute and latent CMV infection. In this review we will discuss the current state of developing RhCMV as a model for HCMV.

Abstract: Adoptive transfer of antiviral effector or memory CD8 T cells is a therapeutic option for preventing acute cytomegalovirus (CMV) disease after primary or recurrent infection in immunocompromised recipients of hematopoietic stem cell transplantation (HSCT) aimed at curing hematopoietic malignancies Preclinical research in murine models has demonstrated the power of CD8 T-cell-based preemptive immunotherapy and has encouraged clinical trials that gave promising results The clinical evidence, however, is based primarily on statistical analyses indicating a reduced incidence of CMV-associated complications Here, we will briefly review the data obtained from the murine model showing that CD8 T cells derived from CMV-immune donors and administered either as peptide-selected cytolytic T lymphocyte lines or after ex vivo purification by T-cell-receptor-specific cell sorting can indeed prevent CMV-mediated histopathology and multiple organ failure

Abstract: Murine cytomegalovirus (MCMV) is a well-studied model of natural β-herpesvirus infection. However, many questions remain regarding its control by and evasion of the immune response it generates. CD8 and CD4 T cells have both unique and redundant roles in control of the virus that differ based on the immunocompetence of the infected mice. MCMV encodes major histocompatibility complex (MHC) class I immune evasion genes that can have an impact in vitro, but their role in infection of immunocompetent mice has been difficult to identify. This review addresses the evidence for their in vivo function and suggests why they may be evolutionarily conserved.

Abstract: Bioinformatic and direct cloning approaches have led to the identification of over 100 novel miRNAs expressed in DNA viruses, although the function of the majority of these small regulatory RNA molecules is unclear. Recently, a number of reports have now identified potential targets of viral miRNAs, including cellular and viral genes as well as an ortholog of an important immuno-regulatory cellular miRNA. In this review, we will cover the identification and characterization of miRNAs expressed in the herpesvirus family and discuss the potential significance of their role in viral infection.

Abstract: Preclinical research in murine models as well as subsequent clinical trials have concordantly revealed a high protective potential of antiviral CD8 T cells, of donor-derived ex vivo memory CD8 T cells in particular, in the immunotherapy of cytomegalovirus (CMV) infection in immunocompromised recipients. Although it is generally held view that the observed beneficial effect of the transferred cells is viral epitope-specific, involving the recognition of MHC class-I presented peptides by cognate T cell receptors, this assumption awaits formal proof, at least with regard to the in vivo function of the CD8 T cells. This question is particularly evident for CMV, since the function of viral immune evasion proteins interferes with the MHC class-I pathway of peptide presentation. Alternatively, therefore, one has to consider the possibility that the requirement for epitope recognition may be bypassed by other ligand-receptor interactions between CD8 T cells and infected cells, which may trigger the signaling for effector functions. Clearly, such a mechanism might explain why CD8 T cells are so efficient in controlling CMV infection despite the expression of viral immune evasion proteins. Here we provide direct evidence for epitope-specificity of antiviral protection by employing a recombinant murine CMV (mCMV), namely the mutant virus mCMV-IE1-L176A, in which an immunodominant viral epitope of the regulatory immediate-early protein IE1 is functionally deleted by a point mutation replacing leucine with alanine at the C-terminal MHC anchor position of the antigenic peptide.

Abstract: Human cytomegalovirus (HCMV) is a ubiquitous pathogen that causes morbidity risk in immunologically suppressed and immunodeficient patients including congenital infections. Approaches to curb the consequences of HCMV infections are restricted by a lack of complete understanding of viral pathogenesis. The infection of mice with murine cytomegalovirus (MCMV) as a model of HCMV infection has been particularly useful in elucidating the role of innate and adaptive immune response mechanisms. A large number of cytomegalovirus genes modulate the innate and the adaptive host immune response. The products of several MCMV genes are involved in subverting the natural killer (NK) cell response by down-modulating cellular ligands for the NKG2D receptor expressed on NK cells and CD8(+) T cells. Mutant viruses lacking these immunoevasion genes are attenuated with respect to virus growth in vivo. Given the importance of the NKG2D receptor in controlling both NK- and T cell-mediated immunity, it is of tremendous importance to understand the molecular mechanisms and consequences of viral regulation of the NKG2D ligands.

Abstract: A vaccine consisting of rhesus cytomegalovirus (RhCMV) pp65-2, gB and IE1 expressed via modified vaccinia Ankara (MVA) was evaluated in rhesus macaques with or without prior priming with expression plasmids for the same antigens. Following two MVA treatments, comparable levels of anti-gB, pp65-2 and neutralizing antibody responses, and pp65-2- and IE1-specific cellular immune responses were detected in both vaccinated groups. Similar reductions in plasma peak viral loads were observed in these groups compared to untreated controls. This study demonstrates the immunogenicity and protective efficacy of rMVA-based RhCMV subunit vaccines in a primate host and warrants further investigation to improve the efficacy of subunit vaccines against CMV.

Abstract: The promise of the mouse model of cytomegalovirus (CMV) research lies in a cost effective way to obtain significant data in in vivo settings. Keeping that promise requires a high degree of equivalency in the human and mouse virus. While genomic structure and many common proteins suggest that this system is appropriate to develop and test concepts in an organismal context, areas of difference have not been evaluated. Here we show that the major immediate early protein 1 (IE1) in MCMV binds the repressor Daxx suggesting that it serves a function performed by pp71 in HCMV. A Daxx binding pp71 equivalent at M82 could not be identified for MCMV. Differences in the mouse and human interferon upregulation of Daxx may have driven the need to have a Daxx-defeating function during reactivation, when pp71 is not present. The major immediate early protein 1 also differs in its chromatin binding properties between the two viruses. MCMV IE1 does not bind to chromatin, but HCMV IE1 does. It remains unclear whether this difference is functionally significant. The HCMV major immediate early protein 2 and its MCMV equivalent IE3 differ in their effect on the cell cycle; HCMV IE2 blocks the cell cycle, but MCMV IE3 does not, allowing MCMV to spread in infected mouse cells by cell division with continued expression of the major transactivating viral proteins. Actively transcribing genomes inducing immediate transcript environments are usually silenced and diminish during cell cycle progression. However, a recognizable desilencing and increase in immediate transcript environments takes place immediately after mitosis in MCMV infected cells. This raises the possibility that desilencing happens during tissue transplantation, wound healing, or other injury where cells are induced to proliferate.

Abstract: Therapy of cytomegalovirus (CMV) infection in recipients of hematopoietic stem cell transplantation (HSCT) by immune serum transfer did not fulfill the high clinical expectations, although immune sera or immunoglobulin-enriched preparations pooled from many CMV-immune donors are likely to contain virus neutralizing antibodies covering a broad range of virus variants. Likewise, the highest risk of CMV disease in HSCT recipients results from the reactivation of the latently infected recipient’s own virus despite pre-transplantation humoral immunity. These findings suggest the conclusion that antiviral antibodies are inefficient in controlling CMV. Rather than B cells and antibodies, T cells, in particular CD8 T cells, are thought to play a major role in resolving established organ infection. In theory, antibodies, though being capable of neutralizing free virions, could fail to prevent cell-bound virus dissemination from the portal of entry to distant target tissues and also could fail in preventing cell-to-cell spread within tissue. Here we have used murine model systems, including B cell deficient C57BL/6 μ− μ− (μMT) mutants, to revisit the role of antiviral antibodies in the control of CMV infection and to reevaluate the prospects of an antibody-based immunotherapy from a basic science point of view.

Abstract: Immediate-early (IE) genes are the first genes to be transcribed during the lytic replication cycle of cytomegaloviruses (CMV), and encode nonstructural proteins, which are assumed to have mainly regulatory functions. The IE proteins may play important roles in the pathogenesis of CMV in vivo, for instance during the establishment of latency and during reactivation. We constructed mouse CMV mutants with disruptions in the major IE genes, ie1 and ie3, to study the roles of these genes in the context of the viral infection. Here we summarize the current results on the characterization of these mutants and give a perspective of the future research in this field.

Abstract: Hematopoietic stem cell transplantation (HSCT) bears a risk of reactivating latent cytomegalovirus (CMV) in either the transplanted hematopoietic donor cells or in parenchymal and stromal tissue cells of the immunocompromised recipient, or in both. While reactivated human CMV in recipients of organ transplantations is frequently the virus variant of the donor, this is not usually the case in HSCT recipients. Here we have used experimental sex-mismatched HSCT in the BALB/c mouse model to test if latent murine CMV from CMV-immune donors is transmitted with bone marrow cells to naive immunocompromised recipients.

Abstract: Gliosis of glial fibrillary acidic protein (GFAP) associated astrocytes is considered to be one of the hallmarks of transmissible spongiform encephalopathies (TSEs). In the present study, remarkable GFAP-PrP(Sc) or GFAP-PrP(C) complexes were separately detected in the brain homogenates of 263 K (Scrapie)-infected or normal hamsters by co-immunoprecipitation assay. To get more exact molecular evidences for interaction between prion protein (PrP) and GFAP, various recombinant PrP or GFAP proteins were expressed using prokaryotic-expressing and in vitro translation system. Using pull down and co-immunoprecipitation assays, reliable molecular interaction between PrP and GFAP was observed, and proteinase K (PK)-digested PrP(Sc) molecules were confirmed to be able to bind the recombinant GFAP specifically as well. The region within PrP that was responsible for interaction with GFAP was narrowed to PK-resistant core of PrP (i.e. aa 91-230). The study of the association of PrP with GFAP supplies the molecular evidence for the observation of co-localization of PrP(Sc) and GFAP in the brains of TSEs and may further provide insight into a potential role of GFAP in the biological function of PrP and the pathogenesis of prion diseases.

Abstract: Development of a vaccine against human cytomegalovirus (HCMV) infection has been identified as a high priority goal in biomedical research, yet no vaccine has been licensed until now. Recombinant subviral dense bodies (recDB) are a promising basis for the establishment of such a vaccine. In this article, strategies for the generation of recDB, based on recombination-mediated genetic engineering of the 230 kb HCMV DNA genome in E. coli are outlined. Analysis of viral mutants that were constructed in this process provided the proof-of-principle that heterologous antigens can be packaged into recDB and that these particles prime CD8 T cell responses against the recombinant antigen upon their application to HLA-A2 transgenic mice.

Abstract: B cells were previously shown to mediate partial protection against CMV infection, as in the absence of B cells, latently infected mice were more susceptible to virus reactivation. It remains unclear if this effect stems from the loss of B cells as antibody producers or as antigen presenting cells. To address this fundamental question, we propose to make use of new mouse models that allow conditional ablation of B cells or that allow for the generation of mice with B cells that are not able to produce antibodies.

Abstract: The aim of this study was to determine the prevalence of varicella IgG antibodies in the population of Catalonia, and the variables associated. The study was carried out in 2002 in a representative sample of juvenile (5-14 years) and adult population (> or =15 years) of Catalonia (Spain). The global prevalence determined by ELISA test was 95.5% (95% CI 94.7-96.3). The prevalence increased with age, from 82% (95% CI 77.0-87.0) in the 5-9 years age up to 99.4% (95% CI 98.2-100) in >64 years of age. No statistically significant differences in the seroprevalence according to the sociodemographic variables were observed. The current strategy of vaccinating preadolescents at 12 years of age who have not suffered the disease will require more than 30 years to cover the current gap immunity in adolescents and young adults. Vaccination with two doses of vaccine for all adolescents and adults < or = 50 years who report not having suffered the disease during childhood should be considered.

Abstract: The human cytomegalovirus (HCMV) is a relevant pathogen in patients with immunosuppressive therapy; however, reactivation and subsequent recurrence occurs also in individuals without canonical immunosuppression as e.g., in patients with septic shock. Analyzing the impact of NK- and T-cell immunity on the natural course of HCMV infection in patients with septic shock, it became clear that the presence of HCMV reactive T-helper cells did not prevent the development of reactivation but, the control of active infection was achieved mostly by specific T-cells. NK-cells seemed to be dispensable for clearance of active infection in this patient group with long-lasting NK-cell anergy.

Abstract: We have isolated a Chikungunya (Chik) virus from a patient who returned to Germany after a three-month visit to Mauritius in spring 2006. Upon return she developed a transient fever up to 40°C. This was followed by myalgia and joint pain. IgG antibodies in serum to Chik virus were undetectable. Virus (Chik-Wu1) was isolated on Vero cells. We molecularly cloned the whole genome of Chik-Wu1 from viral RNA by RT-PCR. The complete sequence was determined and functional domains of the genome were assigned. Chik-Wu1 clearly belongs to the group of viruses analysed from the recent Indian Ocean outbreak. In order to develop tools useful for further characterization of Chik-Wu1, we bacterially expressed and purified the capsid (C) and envelope (E) proteins and established an immunoblot assay. Twenty-two of 30 serum samples from Chik virus-infected patients that scored positive in indirect immunofluorescence previously were also reactive in immunoblot analysis with recombinant C and E2 antigens.

Abstract: Interleukin-8 (IL-8) is an important mediator in neutrophil-mediated acute inflammation but has also a wide range of actions on various cells types. We demonstrated that infection of melanoma cells and fibroblasts with cell-associated varicella-zoster virus (VZV) and infection of a T cell line with cell-free VZV resulted in an induction of IL-8 secretion in vitro. The inhibition of the VZV replication with a drug interfering with its DNA replication had no effect on the IL-8 release. Since the IL-8 promoter contains binding sites for NF-κB and AP-1, melanoma cells and the T cell line were treated with inhibitors of NF-κB, JNK/SAPK or p38/MAPK prior to infection. In melanoma cells, the JNK/SAPK pathway was shown to be important for the IL-8 secretion during the VZV replication, whereas in the T cell line, not only the JNK/SAPK but also the p38/MAPK pathways were required for IL-8 secretion. The neutralisation of the IL-8 bioactivity had no significant consequence on the VZV replication, suggesting that IL-8 acts neither as a proviral nor as an antiviral cytokine during the VZV replication in vitro.

Abstract: IbeT is a downstream gene of the invasion determinant ibeA in the chromosome of a clinical isolate of Escherichia coli K1 strain RS218 (serotype 018:K1:H7). Both ibeT and ibeA are in the same operon. Our previous mutagenesis and complementation studies suggested that ibeT may coordinately contribute to E. coli K1 invasion with ibeA. An isogenic in-frame deletion mutant of ibeT has been made by chromosomal gene replacement with a recombinant suicide vector carrying a fragment with an ibeT internal deletion. The characteristics of the mutant in meningitic E. coli infection were examined in vitro [cell culture of human brain microvascular endothelial cells (HBMEC)] and in vivo (infant rat model of E. coli meningitis) in comparison with the parent strain. The ibeT deletion mutant was significantly less adhesive and invasive than its parent strain E. coli E44 in vitro, and the adhesion- and invasion-deficient phenotypes of the mutant can be complemented by the ibeT gene. Recombinant IbeT protein is able to block E. coli E44 invasion of HBMEC. Furthermore, the ibeT deletion mutant is less capable of colonizing intestine and less virulent in bacterial translocation across the blood–brain barrier (BBB) than its parent E. coli E44 in vivo. These data suggest that ibeT-mediated E. coli K1 adhesion is associated with the bacterial invasion process.

Abstract: Hematopoietic stem cell transplantation (HSCT) is a promising therapeutic option against hematopoietic malignancies. Infection with cytomegalovirus (CMV) and tumor relapse are complications that limit the success of HSCT. In theory, CMV infection can facilitate tumor relapse and growth by inhibiting “graft take” and reconstitution of the immune system or by inducing the secretion of tumor cell growth-promoting cytokines. Conversely, one can also envisage an anti-tumoral effect of CMV by cytopathic/oncolytic infection of tumor cells, by inducing the secretion of death ligands for tumor cell apoptosis, and by the activation of systemic innate and adaptive immunity. Here we will briefly review the current knowledge about tumor control in a murine model of CMV infection and liver-adapted B cell lymphoma, with a focus on a putative implication of CD49+NKG2D+ hepatic natural killer cells.

Abstract: Respiratory syncytial virus (RSV) infection is ubiquitous and leads to various outcomes between immunocompetent and immunocompromised individuals. This study aimed to compare RSV infection and inflammatory responses between immunocompetent BALB/c mice and immunodeficient nude mice. RSV titers in both infected BALB/c mice and nude mice peaked on the third day post-inoculation, but the nude mice had longer lasting and higher levels of viral replication. RSV infection induced a more severe grade of pulmonary histopathology and larger numbers of leukocytes in airways of nude mice than that of BALB/c mice. RSV infection increased pulmonary macrophages and natural killer (NK) cells in both strains of mice. Furthermore, infected nude mice had larger numbers of pulmonary macrophages and NK cells than infected BALB/c mice. Whereas the RSV infected BALB/c mice secreted more tumor necrosis factor –α (TNF-α), interleukin-12 (IL-12), interferon-γ (IFN-γ) and IL-10 than control BALB/c mice, the infected nude mice had higher levels of TNF-α, IL-12 and IL-10 than the infected BALB/c mice. The inflammation induced by RSV infection did not correspond with the immune response of T cells. Macrophages and NK cells were potent immunocytes and inflammatory cells in RSV infection especially when T lymphocytes were deficient. Therefore, nude mice may be a good model for severe and persistent RSV infection in immunocompromised hosts.

Abstract: Vibrio cholerae cytolysin (VCC) is a pore-forming toxin that is secreted in precursor form (pro-VCC) and requires proteolytic cleavage in order to attain membrane-permeabilizing properties. Pro-VCC can be activated both in solution and membrane-bound state. Processing of membrane-bound pro-VCC can in turn be achieved through the action of both cell-associated and soluble proteases. The current investigation describes the interaction of VCC with human neutrophil granulocytes. It is shown that pro-VCC binds to these cells and is cleaved by cell-bound serine proteases. Membrane permeabilization leads to granulocyte activation, as witnessed by the generation of reactive oxygen metabolites and liberation of granule constituents. A mutant toxin with unaltered binding properties but devoid of pore-forming activity did not elicit these effects. The secreted proteases cleave and activate further bound- and non-bound pro-VCC. A positive feedback loop is thus created that results in enhanced cytotoxicity towards both the targeted granulocytes and towards bystander cells that are not primarily killed by the protoxin. Thus, activation of neutrophil granulocytes by VCC fuels a positive feedback cycle that will cripple immune defence, augment inflammation, and enhance the cytotoxic action of the toxin on neighbouring tissue cells.

Abstract: Control of human cytomegalovirus (HCMV) infection and prevention of associated diseases in immunocompetent hosts are ensured mainly by CD8+ T cells, in spite of numerous viral tricks to impair antigen presentation and activation of T cells. At sites of primary infection, dendritic cells (DCs) are in the forefront to ensure capture of viral antigens and their capacity to bypass the effects of viral immunoevasins is crucial in moulding CD8+ T cell repertoire. In HCMV-seropositive donors, the spectrum of CD8+ T cells specificities was shown to include immediate-early (IE), early (E) and late (L) gene products, a surprising finding if we consider that expression of immunoevasins could paralyse infected DCs from the IE phase of infection. In the present report, we suggest that uninfected dendritic cells could acquire HCMV-antigens derived from input virus or neosynthesis, either in soluble forms or in association with infected dead cells resulting from death-ligand-mediated apoptosis and necrosis. Activation of naive CD8+ T cells could then occur in lymph nodes through cross-presentation by antigen-loaded DCs, providing an explanation for shape and size of the memory compartment.

Abstract: We present a systematic study that defines molecular profiles of adjuvanticity and pyrogenicity induced by agonists of human Toll-like receptor molecules in vitro Using P3CSK4, Lipid A and Poly I:C as model adjuvants we show that all three molecules enhance the expansion of IFNγ+/CD4+ T cells from their naive precursors following priming with allogeneic DC in vitro In contrast, co-culture of naive CD4+ T cells with allogeneic monocytes and TLR2/TLR4 agonists only resulted in enhanced T cell proliferation Distinct APC molecular signatures in response to each TLR agonist underline the dual effect observed on T cell responses Using protein and gene expression assays, we show that TNF-α and CXCL10 represent DC-restricted molecular signatures of TLR2/TLR4 and TLR3 activation, respectively, in sharp contrast to IL-6 produced by monocytes upon stimulation with P3CSK4 and Lipid A Furthermore, although all TLR agonists are able to up-regulate proIL-1β specific gene in both cell types, only monocyte activation with Lipid A results in detectable IL-1β release These molecular profiles, provide a simple screen to select new immune enhancers of human Th1 responses suitable for clinical application

Abstract: Infections with cytomegaloviruses are characterized by an intricate balance between the expression of immunomodulatory viral proteins and antiviral immune defence. For human cytomegalovirus (HCMV), several proteins have been described that interfere with the recognition of infected cells by CD8 T lymphocytes. Although the modes of action of these proteins have been elucidated on the molecular level, thus rendering them useful models to understand MHC class I peptide loading and transport, their role during viral infection has remained enigmatic. We exemplify here, how HCMV mutants can help to understand the importance of individual immunomodulatory proteins in the context of viral infection.

Abstract: Dendritic cells (DCs) are the most powerful antigen presenting cells (APCs) in the immune system. Therefore, they are able to take up antigen by phagocytosis, macropinocytosis or endocytosis, process it in the cytosol and present it to naive T cells. It is known that presentation of the immunodominant influenza virus nucleoprotein-derived CTL epitope is delayed in bone marrow-derived DCs (BMDCs) compared to non-professional APCs. This delay coincided with the formation of transient aggregations of ubiquitinated proteins (DALIS, dendritic cell aggresome-like induced structures), which contain probably defective ribosomal products (DRiPs). DRiPs appear in the cytosol of maturing DCs and macrophages. Normally, DRiPs are degraded rapidly by proteasomes. However, their storage in DALIS delays their degradation. So, it is hypothesized that DALIS can function as antigen depots allowing DCs to coordinate maturation and antigen presentation during their migration to the lymph nodes. Upon inhibition of several pathways among the in signal transduction pathways of DCs, like the phosphatidylinositol 3-kinase (PI3-K) or the mammalian target of Rapamycin (mTOR), the cells show a rendered maturation profile. The formation of DALIS is inhibited in these cells which can be expected to influence antigen processing and presentation.

Abstract: The cAMP-dependent protein kinase A (PKA) is a key enzyme for many cellular mechanisms. In this study, we investigated the importance of this kinase for the replication of the alphaherpesvirus Varicella-zoster virus (VZV). We report that the expression of the catalytic subunit of PKA was strongly increased at the beginning of the viral cycle. The presence of a peptide inhibitor of PKA had no consequence on viral replication in a melanoma cell line whereas in fibroblasts, it resulted in a drastic decrease of replication. An overall analysis of PKA substrates phosphorylation patterns during VZV replication showed that the phosphorylation of PKA substrates was modulated. These results were completed by investigating the accumulation and phosphorylation patterns of the PKA target cAMP response element binding protein (CREB). This transcription factor remained available throughout the VZV replication, but its phosphorylation decreased in the early phase of infection before it rose later on. These results indicate that the PKA signalling plays a cell-type dependent role for VZV replication and that the infection resulted in a regulated CREB-dependent gene expression.

Abstract: There are no recommendations concerning preoperative management of primary immunodeficiency patients in cases of emergency or planned surgery in relation to risk of hepatitis type B virus infection. To assess if immunodeficient patients regularly supplemented with immunoglobulins are protected against hepatitis B. IgG, IgM and IgA total levels and anti-HBs level were estimated in adult patients with primary humoral immunodeficiency before and after immunoglobulins supplementation according to a standardized schedule. Serum IgG and anti-HBs level significantly increased after immunoglobulin supplementation. Anti-HBs titer increased in all cases over 100 IU/L regardless of initial total IgG serum value, reaching a highly protective level. There was no correlation between increase in concentration of IgG (ΔIgG) versus Δanti-HBs in the studied patients. Patients with primary hypogammaglobulinemia supplemented with immunoglobulin are protected against hepatitis type B.

Abstract: Primary human cytomegalovirus (HCMV) infection of an immunocompetent individual leads to the generation of a robust CD4+ and CD8+ T cell response which subsequently controls viral replication. HCMV is never cleared from the host and enters into latency with periodic reactivation and viral replication, which is controlled by reactivation of the memory T cells. In this article, we discuss the magnitude, phenotype and clonality of the T cell response following primary HCMV infection, the selection of responding T cells into the long-term memory pool and maintenance of this memory T cell population in the face of a latent/persistent infection. The article also considers the effect that this long-term surveillance of HCMV has on the T cell memory phenotype, their differentiation, function and the associated concepts of T cell memory inflation and immunosenescence.