Christian A. García-Sepúlveda

Influence of human cytomegalovirus infection on the NK cell receptor repertoire in children

Human cytomegalovirus (hCMV) infection is usually asymptomatic but may cause disease in immunocompromised hosts. It has been reported that hCMV infection may shape the NK cell receptor (NKR) repertoire in adult individuals, promoting a variable expansion of the CD94/NKG2C+ NK cell subset. We explored the possible relationship between this viral infection and the expression pattern of different NKR including CD94/NKG2C, CD94/NKG2A, immunoglobulin‐like transcript 2 (ILT2, CD85j), KIR2DL1/2DS1, KIR3DL1, and CD161 in peripheral blood lymphocytes from healthy children, seropositive (n=21) and seronegative (n=20) for hCMV. Consistent with previous observations in adults, a positive serology for hCMV was associated with increased numbers of NKG2C+ NK and T cells as well as with ILT2+ T lymphocytes. Moreover, the proportions of CD161+ and NKG2C+CD56−CD3− NK cells also tended to be increased in hCMV+ individuals. Excretion of the virus was associated with higher proportions of NKG2C+ NK cells. Altogether, these data reveal that hCMV may have a profound influence on the NKR repertoire in early childhood.

Severe pneumonia associated with pandemic (H1N1) 2009 outbreak, San Luis Potosí, Mexico.

Severe pneumonia developed in young adults who had no identifiable risk factors.

Impact of early developmental arsenic exposure on promotor CpG-island methylation of genes involved in neuronal plasticity

Epigenetic mechanisms are crucial to regulate the expression of different genes required for neuronal plasticity. Neurotoxic substances such as arsenic, which induces cognitive deficits in exposed children before any other manifestation of toxicity, could interfere with the epigenetic modulation of neuronal gene expression required for learning and memory. This study assessed in Wistar rats the effects that developmental arsenic exposure had on DNA methylation patterns in hippocampus and frontal cortex. Animals were exposed to arsenic in drinking water (3 and 36ppm) from gestation until 4 months of age, and DNA methylation in brain cells was determined by flow cytometry, immunohistochemistry and methylation-specific polymerase chain reaction (PCR) of the promoter regions of reelin (RELN) and protein phosphatase 1 (PP1) at 1, 2, 3 and 4 months of age. Immunoreactivity to 5 methyl-cytosine was significantly higher in the cortex and hippocampus of exposed animals compared to controls at 1 month, and DNA hypomethylation was observed the following months in the cortex at high arsenic exposure. Furthermore, we observed a significant increase in the non-methylated form of PP1 gene promoter at 2 and 3 months of age, either in cortex or hippocampus. In order to determine whether this exposure level is associated with memory deficits, a behavioral test was performed at the same age points, revealing progressive and dose-dependent deficits of fear memory. Our results demonstrate alterations of the methylation pattern of genes involved in neuronal plasticity in an animal model of memory deficit associated with arsenic exposure.

Killer-cell immunoglobulin-like receptors (KIR) in severe A (H1N1) 2009 influenza infections

Introduction of a novel influenza virus into the human population leads to the occurrence of pandemic events, such as the one caused by pandemic influenza A (H1N1) 2009 virus. The severity of infections caused by this virus in young adults was greater than that observed in patients with seasonal influenza. Fatal cases have been associated with an abnormal innate, proinflammatory immune response. A critical role for natural killer cells during the initial responses to influenza infections has been suggested. In this study, we assessed the association of killer-cell immunoglobulin-like receptors (KIRs) with disease severity by comparing KIR gene content in patients with mild and severe pandemic influenza virus infections to a control group. We found that activator (KIR3DS1 and KIR2DS5) and inhibitory (KIR2DL5) genes, encoded in group B haplotypes containing the cB01, cB03 and tB01 motifs, are associated with severe pandemic influenza A (H1N1) 2009 infections. Better understanding of how genetic variability contributes to influenza virus pathogenesis may help to the development of immune intervention strategies aiming at controlling the severity of disease.

Pandemic influenza A(H1N1) 2009 and respiratory syncytial virus associated hospitalizations

OBJECTIVES To determine the contribution of influenza and respiratory syncytial virus (RSV) as the cause of lower respiratory tract infection (LRTI) associated hospitalizations during the first year of the influenza A(H1N1) 2009 pandemic and to assess the severity of illness during the second pandemic wave. METHODS Patients admitted with LRTI from April 2009 through March 2010 were assessed for the presence of influenza and RSV. Pandemic influenza virus was detected by means of a nested RT-PCR assay and/or the CDCs real time-PCR protocol. RSV was detected using a one-step RT-PCR assay. The characteristics of patients admitted during the first and second pandemic outbreaks were compared. RESULTS 657 patients with LRTI were admitted during the study period. Pandemic influenza virus was detected in 180 and RSV in 133. Influenza was the most common cause of infection in adults, while RSV was more common in children. There were no differences in disease severity between the first and second pandemic outbreaks. CONCLUSIONS Pandemic influenza virus was associated to increased numbers of hospitalizations and deaths; particularly in adults. The severity of the first and second pandemic outbreaks was similar. RSV continues to be the main pathogen responsible for hospitalizations in young children.

KIR gene diversity in Mexican mestizos of San Luis Potosí

Natural killer (NK) cell function is regulated by different types of membrane-bound receptors of which killer-cell immunoglobulin-like receptors (KIRs) are the most complex and diverse. KIRs are encoded by 17 different genes located within the leukocyte receptor complex (19q13.4). The frequency with which KIR gene features are present in different human populations differs. Here, we present our results on the KIR gene diversity observed in a large group of mestizos from the central Mexican city of San Luis Potosí. In total, 53 different KIR genotypes were observed, 47 with previously described gene profiles and six harboring novel KIR gene combinations. Group A homozygous haplotypes were seen in 102 individuals (34%), while group B homozygous haplotypes were present in 45 (15%). Heterozygous combinations of groups A and B haplotypes were seen in 153 individuals (51%). Haplotype frequency estimations based on a true content of 600 chromosomes showed a relatively balanced proportion of group A (59.5%) and group B (40.5%) haplotypes in our study population. A homozygous combination of the cA01|tA01 haplotype was present in 33% of the population with other frequent combinations being cA01|tA01, cB03|tB01 in 14.7% and cA01|tA01, cB02|tA01 in 12%. The dendrogram derived from activating KIR gene phylogenetic analysis revealed five clearly distinct clades corresponding to African, East Asian, Arab/Caucasoid, Mexican mestizo/Amerindian and South Asian populations. Our results illustrate the genetic contribution that Caucasoid and Amerindian populations have made toward present-day Mexicans and suggest an important Southeast Asian genetic contribution to native Amerindian populations.

NKG2C gene deletion in the Mexican population and lack of association to respiratory viral infections

Expansion of a natural killer (NK) cell population that expresses NKG2C has been associated with cytomegalovirus and other viral infections. It has been suggested that this cell population may play a role in infection control. Deletion of the NKG2C gene (homozygous or heterozygous) has been reported with high prevalence in European and Asian populations. However, the effect of NKG2C genotype on NK cell responses to infection remains poorly defined. We determined the prevalence of the NKG2C deletion in a Mexican population (n = 300) and in a group of patients (n = 131) to assess whether NKG2C genotype affects the incidence of symptomatic viral infections caused by influenza or respiratory syncytial virus. The frequency of the NKG2C deletion haplotype in Mexican mestizos was significantly lower (10.3%) than that reported in other populations (17.5–21.9%). No difference in the prevalence of NKG2C deletion was observed in subjects with viral infections compared with the reference population. In addition, no differences in clinical characteristics and infection outcome were observed between patients with and without the NKG2C gene deletion. Our results indicate that copy number variation in the NKG2C gene has no impact on the severity of respiratory viral infections.

Effect of an immunization program on seasonal influenza hospitalizations in Mexican children

We analyzed 2378 respiratory samples of children <5 years of age admitted during a 7-year period in order to determine the contribution of seasonal influenza as a cause of hospitalizations, as well as the impact of the inclusion of influenza vaccine in the childhood immunization program. The presence of influenza virus was demonstrated in 106 (4.4%) samples. The proportion of influenza hospitalizations after the introduction of influenza vaccination was lower (3.4%) than before the establishment of this vaccination program (7.5%; P=0.00002). Our study shows that influenza vaccination programs in children significantly reduce the impact of influenza related hospitalizations.

Mortality attributable to pandemic influenza A (H1N1) 2009 in San Luis Potosí, Mexico

Please cite this paper as: Comas‐García et al. (2011) Mortality attributable to pandemic influenza A (H1N1) 2009 in San Luis Potosí, Mexico. Influenza and Other Respiratory Viruses 5(2), 76–82.

Infección congénita por citomegalovirus en recién nacidos del estado de San Luis Potosí, México

Objective. To determine the prevalence of congenital cytomegalovirus infection in newborn infants included in the neonatal screening program coordinated by the State Health Services in San Luis Potosi. Material and Methods. We evaluated the presence of cytomegalovirus in blood samples stored in filter paper. Results. Cytomegalovirus was detected in 10 (0.68%) of the 1 457 samples included in the study. There were no differences in the characteristics of infants with congenital infection compared to those without infection. Conclusions. It is necessary to increase awareness of health professionals regarding the prevalence and impact of congenital cytomegalovirus infection.