Maternal reinfection by new strains of cytomegalovirus is a major source of congenital infection in this population.

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Survivors from sepsis are in an immunosuppressed state that is associated with higher long-term mortality and risk of opportunistic infections. Whether these factors contribute to neoplastic proliferation, however, remains unclear. Tumorassociated macrophages (TAM) can support malignant cell proliferation, survival, and angiogenesis. We addressed the relationship between the post-sepsis state, tumor progression and TAM accumulation, and phenotypic and genetic profile, using a mouse model of sepsis resolution and then B16 melanoma in mice. In addition, we measured the serum concentrations of TNFa, TGFb, CCL2, and CXCL12 and determined the effect of in vivo CXCR4/CXCL12 inhibition in this context. Mice that survived sepsis showed increased tumor progression both in the short and long term, and survival times were shorter. TAM accumulation, TAM local proliferation, and serum concentrations of TGFb, CXCL12, and TNFa were increased. Na€ ve mice inoculated with B16 together with macrophages from post-sepsis mice also had faster tumor progression and shorter survival. Post-sepsis TAMs had less expression of MHC-II and leukocyte activation-related genes. Inhibition of CXCR4/CXCL12 prevented the post-sepsis-induced tumor progression, TAM accumulation, and TAM in situ proliferation. Collectively, our data show that the post-sepsis state was associated with TAM accumulation through CXCR4/ CXCL12, which contributed to B16 melanoma progression.

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Interleukin-18 (IL-18) and interferon-gamma (IFN-γ) exert important functions in both innate and adaptive immune responses against intracellular pathogens and viruses. Previous studies suggested that host genetic factors, including cytokines gene polymorphisms, could be involved in the pathogenesis of human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Thus, we analyzed -137C/G and -607A/C of the IL-18 promoter and +874T/A of the IFN-γ in DNA samples from 98 HTLV-1-infected individuals exhibiting or not clinical symptoms and 150 healthy control individuals. The IL-18 promoter -607CC genotype was significantly lower in HTLV-1 asymptomatic carriers (HAC) and HTLV-1-infected individuals (HAC + HAM/TSP) than healthy control group. In contrast, the -607AC genotype was significantly higher in HAC and HTLV-1-infected individuals group compared to the healthy control group. The -137G/-607A IL-18 haplotype was higher in infected group than healthy control group, and the -137C/-607C IL-18 haplotype was increased in the healthy control group compared to the others. Finally, the IFN-γ polymorphism analysis showed that the HTLV-1-infected individuals with +874AT genotype presented higher proviral load than +874AA genotype. These data indicate that the IL-18-607AC genotype and -137G/-607A haplotype could be a risk factor for HTLV-1 infection, whereas the protective effect could be conferred by -607CC genotype and -137C/-607C haplotype. Also, the IFN-γ could be implicated on the proviral load levels.

A case-control study design was used in order to compare the distribution of human cytomegalovirus (HCMV) glycoprotein B (gB) genotypes in 48 mothers of 49 congenitally infected infants with that observed in 144 mothers of 146 uninfected infants to study genetic variation of HCMV strains and maternal-fetal transmission. Congenital infection with HCMV was characterized by DNA detection and virus isolation from two urine or saliva samples collected prior to the third week of life. Genotyping of HCMV was carried out by a polymerase chain reaction-restriction fragment length polymorphism analysis of the variable region of the gB gene, testing for four genotypes. Genotype frequency was similar among the 28 non-transmitting mothers who were shedding virus (gB1: 25%; gB2: 28.6%; gB3: 42.8%; gB4: 0%), the 37 transmitting mothers (gB1: 21.6%; gB2: 46%; gB3: 27%; gB4: 0%), and the 49 infected infants (gB1: 39%; gB2: 37%; gB3: 24%; gB4: 0%). The same genotype was detected at different body sites (urine, saliva, and blood) of each infected newborn and in the respective mother (breast milk, urine, and saliva). Co-infection with multiple genotypes was observed in the immediate postpartum period in two mothers of infected infants (5.4%) and one non-transmitting mother (3.6%). The gB genotype was not correlated with intrauterine HCMV transmission. The genotype distribution found reflects the overall frequency of wild strains circulating in this geographic region. A single genotype is responsible for congenital HCMV infection. Co-infection with more than one strain, as characterized by gB genotype, was infrequent in women who were presumably immunocompetent.

No abstract

The role of the human cytomegalovirus (HCMV) infection in individuals with hemoglobinopathies is unclear. Our objective was to examine the molecular and genotypic characteristics of HCMV in patients with sickle cell disease, beta-thalassemia major, and volunteer blood donors by viral load quantitation, glycoprotein B (gB) genotyping, and phylogenetic analysis. The patients with sickle cell disease demonstrated the highest HCMV DNA prevalence (13.8%), followed by the patients with beta-thalassemia major (7.6%), and the blood donors (3%). The infection was characterized by a low mean viral load (3.8×10(3) copies/mL), but infections with higher copy numbers were also observed. Genotype gB2 was detected in the majority of cases (90.9%), followed by genotype gB1 (9.1%). No gB3/gB4 genotype was detected. No statistical significance was observed between HCMV DNAemia/gB genotype and hematological alterations or severity of the disease. The high number of sickle cell disease patients with HCMV DNAemia could be due to their partial immune dysfunction (multiple transfusions, spleen dysfunction, hydroxyurea treatment). The extensive HCMV gB2 prevalence in patients with hemoglobinopathies is probably due to HCMV epidemiologic characteristics in the examined region, and can be important during the clinical management of these patients.