HHV-6 IgG4 isotype response following measles infection.

Human herpesvirus 6 (HHV-6) is widespread in the human population by infecting most individuals in early childhood. After primary infection, HHV-6 establishes a latent infection by remaining in circulating mononuclear cells of healthy individuals. The HHV-6 antibody titer increases after primary infection with measles virus. The present study was undertaken to determine the specific antiviral IgG1, IgG2, IgG3, and IgG4 subclass response patterns to HHV-6 in HHV-6-seropositive individuals with natural measles virus infection, measles vaccination, and rubella virus infection. The purpose of this study was to examine HHV-6-specific IgG isotype response in patients with acute virus coinfection. Serum samples were obtained from individuals who were seropositive for HHV-6 after natural primary infection with measles virus during an outbreak, measles vaccination, or rubella virus infection, and from healthy individuals. Sera were examined by indirect immunofluorescence assays for detection of HHV-6-specific IgG1, IgG2, IgG3, and IgG4 antibodies. A high percentage (69%) of those infected with measles virus had an HHV-6 IgG1 and IgG4 response (P < 0.001, chi(2) test), whereas persons vaccinated against measles, those infected with rubella, and healthy individuals showed an HHV-6 IgG1 response. These results demonstrate that natural measles virus infection induces an HHV-6 IgG isotype response, which suggests a shift in immune activity from a Th1 to a Th2 response. J. Med. Virol. 82:396-399, 2010. (c) 2010 Wiley-Liss, Inc.

IgG subclasses and DNA detection of HHV-6 and HHV-7 in healthy individuals.

Human herpesvirus 6 (HHV-6) and 7 (HHV-7) are common opportunistic agents in immunocompromised hosts, although infection with HHV-6 and HHV-7 can also be observed in immunocompetent hosts. Despite similar biology and epidemiology, this study evaluated differences in the IgG subclass distribution associated with HHV-6 and HHV-7 in seropositive, healthy persons. The identified subclasses were also compared with the detection of HHV-6 and HHV-7 DNA. For these assays, sera, plasma, and saliva samples were obtained from 40 healthy blood donors in Argentina who were seropositive for both HHV-6 and HHV-7. HHV-6 and HHV-7 DNA were detected in saliva and plasma samples using nested PCR, and specific IgG subclasses were determined using immunofluorescent assays of sera samples. HHV-7 DNA was detected in 90% of all plasma samples and in 100% of saliva samples. In contrast, HHV-6 DNA was not detected in any of the plasma samples, and it was detected in only 6 of 40 saliva samples. Determination of IgG subclass distributions showed that HHV-6 was restricted to IgG1, whereas HHV-7 IgG subclasses included two groups, one restricted only to IgG1 and the other to IgG1 and IgG3. These results demonstrate the differences between HHV-6 and HHV-7 DNA range detection in saliva and plasma samples, as well as the IgG subclass patterns for each virus type, in healthy persons in Argentina.

A novel human adenovirus hexon protein of species D found in an AIDS patient.

To date, human adenoviruses are classified into 53 types (types 1-51 and types 53 and 54), which have been grouped into six species named A through F, and the recently identified type 52 has been proposed as member of a new species, G. Type classification is based on type-specific epitopes within loop 1 (L1) and loop 2 (L2) of the hexon protein, which contain seven hypervariable regions that are responsible for type specificity. In this paper, we present the characterization of an adenovirus strain isolated from a male AIDS patient in Cordoba, Argentina. This strain was found to be a member of species D by genomic Sma I restriction analysis. Sequencing of the L1 and L2 regions of the hexon gene and immunological characterization by virus neutralization revealed this hexon to be unique and distinct from the previously identified hexons of types within species D. A seroepidemiologic study in the human population of Cordoba showed that this strain was not endemic in the local human population.

Detection of human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7) DNA in endocervical samples from a positive and negative HPV woman of Córdoba, Argentina.

AIMS: The purpose of the present study was to elucidate the presence of human herpesvirus 6A (HHV-6A), HHV-6B and HHV-7 in samples of the uterine cervix through detection of viral DNA. We analysed normal tissues, samples with low-grade squamous intraepithelial lesions (LSILs) and high-grade squamous intraepithelial lesions (HSILs). We correlated the presence of HHV-6 and HHV-7 with the finding of human papillomavirus (HPV) in mucosal samples. METHODS: Cervical samples were examined and grouped as follows: group 1 (n=29), normal cytology; group 2 (n=61), samples with LSIL; group 3 (n=35), samples with HSIL. Molecular biology examinations were performed in all samples to detect HHV-6, HHV-7 and HPV DNA and to typify HHV-6 species. RESULTS: Group 1: normal cytology and HPV (-): HHV-6: 6.8% (2/29), HHV-7: 79.3% (23/29); group 2: LSIL and HPV (-): HHV-6: 93.1% (27/29), HHV-7: 96.5% (28/29); LSIL and HPV (+): HHV-6: 0% (0/32), HHV-7: 90.6% (29/32); group 3: HSIL and HPV (-): HHV-6: 20% (2/10), HHV-7: 70% (7/10); HSIL HPV (+): HHV-6: 12% (3/25), HHV-7: 68% (17/25). HHV-6A DNA was not detected in any samples. CONCLUSIONS: (1) Both HHV-6 and HHV-7 infect the mucosal cells of the cervix with higher prevalence of HHV-7. (2) The higher prevalence of HHV-6 in LSIL HPV (-) samples compared with those with normal cytology indicates that it constitutes a possible risk factor for atypia production. (3) The presence of HHV-7 in all samples questions its role in the production of atypia. (4) The finding of HHV-6 and HHV-7 suggests that the cervical mucosa is a possible transmission pathway for these viruses.

Age-Related Patterns of DNA Detection and Specific IgG Subclasses in Healthy HHV-6- and HHV-7-Infected Individuals.

Human herpesvirus 6A (HHV-6A), Human herpesvirus 6B (HHV-6B), and Human herpesvirus 7 (HHV-7) can persist by establishing a lifelong infection which could have implications on the immunocompetent host. The aim of this work is to contribute with some knowledge about the HHV-6 A/B and HHV-7 infection in healthy individuals. We have carried out a longitudinal study in seropositive healthy individuals for the detection of viral DNA in saliva and plasma samples, and for determining a specific IgG isotype immune response, which enabled the performance of these viruses to be observed over time. Furthermore, an elderly population was transversely studied to provide data of the activity of these viruses in the older population. In the longitudinal study, HHV-6 DNA was occasionally detected and an isotype immune response with a specific IgG1 profile, while in the older group HHV-6 DNA was frequently detected and an isotype immune response with specific IgG1, IgG3, and IgG4. HHV-7 DNA was frequently detected in both groups and isotype patterns of specific IgG1, IgG3, and IgG4. The results of this study highlight that the long-lasting relationship in healthy HHV-6 A/B-infected individuals have the imprint of age groups.

Searching variables to assess recreational water quality: the presence of infectious human enterovirus and its correlation with the main variables of water pollution by multivariate statistical approach in Córdoba, Argentina.

Surface waters are used by local populations for different purposes, such as recreational activities, water source for human and animal consumption, and irrigation among others, which lead to the need for management strategies on water health and associated risks. During this study, we investigated physicochemical parameters, fecal coliform bacteria, and infectious human enterovirus detection to determine the water quality in different beaches (categorized as an urban area, non-urban areas, and an intermediate position) from San Roque Dam, in Argentina. Multivariate techniques were applied. Principal component analysis allowed identification of subgroup of variables responsible for the water quality. A cluster analysis and multivariate analysis of variance showed the urban beach as the highest pollution area. The following variables (measured at the urban beach) would be enough to describe the quality of the aquatic body: nitrites, fecal coliforms, total phosphorous, and infectious human enterovirus. The infectious human enterovirus was an independent variable detected in 69.1% of the samples showing a steady frequency of detection during the whole period studied and could identify human fecal contaminations as a source of water pollution. The selected variables would contribute to water quality regarding the risk for human health using San Roque dam waters for recreational propose.

Genomic analysis of a large set of currently-and historically-important human adenovirus pathogens.

Human adenoviruses (HAdVs) are uniquely important "model organisms" as they have been used to elucidate fundamental biological processes, are recognized as complex pathogens, and are used as remedies for human health. As pathogens, HAdVs may effect asymptomatic or mild and severe symptomatic disease upon their infection of respiratory, ocular, gastrointestinal, and genitourinary systems. High-resolution genomic data have enhanced the understanding of HAdV epidemiology, with recombination recognized as an important and major pathway in the molecular evolution and genesis of emergent HAdV pathogens. To support this view and to actualize an algorithm for identifying, characterizing, and typing novel HAdVs, we determined the DNA sequence of 95 isolates from archives containing historically important pathogens and collections housing currently circulating strains to be sequenced. Of the 85 samples that were completely sequenced, 18 novel recombinants within species HAdV-B and D were identified. Two HAdV-D genomes were found to contain novel penton base and fiber genes with significant divergence from known molecular types. In this data set, we found additional isolates of HAdV-D53 and HAdV-D58, two novel genotypes recognized recently using genomics. This supports the thesis that novel HAdV genotypes are not limited to "one-time" appearances of the prototype but are of importance in HAdV epidemiology. These data underscore the significance of lateral genomic transfer in HAdV evolution and reinforce the potential public health impact of novel genotypes of HAdVs emerging in the population.

Author Correction: Genomic analysis of a large set of currently-and historically-important human adenovirus pathogens.

The original publication of this article [1] was missing the below author that made contributions to the research and the published article.

Long-lasting poliovirus-neutralizing antibodies among Argentinean population immunized with four or five oral polio vaccine doses 1 month to 19 years previously.

The persistence of poliovirus-neutralizing antibodies was investigated in 297 individuals residing in Argentina who had completed the vaccination cycle with four or five oral polio vaccine (OPV) doses 1 mo to 19 yr before this study. Seropositivity for the three polio types in individuals who had received four OPV doses remained high and stable, showing rates not less than 94.6, 98.2, and 91.1% for types 1, 2, and 3, respectively, for a period of at least 6 yr. Almost identical rates were found in children who completed a vaccination schedule of five OPV doses 1 to 2 yr earlier. However, humoral immunity to poliovirus types 3 and 1 declined significantly 9 and 17 yr, respectively, after the booster dose had been administered; in contrast, type 2 immunity remained fairly stable during the 19-yr study period. Overall, geometric mean titer values for poliovirus types 1 and 2 were higher than those for poliovirus type 3. This is likely a result of low initial poliovirus type 3 antibody titers that eventually fell below the limits of detection at later time points. The results indicate that although antibody titers primed by OPV decline over time, they are remarkably long-lived, immunity to poliovirus types 1 and 2 being more prevalent than that against type 3 at late intervals postvaccination.

Measles virus-specific IgG4 antibody titer as a serologic marker of post-vaccinal immune response.

In previous research, we concluded that measles virus specific IgG4 antibody titer could be used to differentiate between natural [IgG4 GMT 80 (95% CI, 33 to 191)] and vaccinal source of measles infection [IgG4 GMT 13 (95% CI, 7 to 26)]. The aim of this paper is to show that this new serologic marker (IgG4 measles antibody titer) can be applied to help interpret rare but well documented cases of measles Ig M-positive results in vaccinated individuals who, 1-2 months after vaccination, developed rash and fever and therefore do not meet the criteria for post-vaccinal measles infection. Six measles IgM-positive serum samples obtained from measles vaccinated individuals who developed rash/fever 1 to 2 months post-vaccination were studied by Immunofluorescence assay for the quantification of IgG4 measles specific antibody. IgG4 antibody titers from all these samples were between 1:10-1:20, consequently, the IgM positive results from the study cases could be ascribed to post-vaccinal immune response. Thus, measles virus specific IgG4 antibody titer could be used as a serologic marker of post-vaccinal immune response.

Loss of maternally-derived human herpesvirus-7 immunity and natural infection in Argentinian infants.

BACKGROUND: Human herpes virus-7 (HHV-7) infection is widespread throughout the world. No data are available in Argentina about loss of maternally-derived HHV-7 immunity and natural infection. OBJECTIVES: The objective of this study was to characterize the time when children lose maternal antibodies and become susceptible to natural infection. METHODS: Sera from 39 pregnant women and 207 infants between 2 and 29 months of age were tested. Determination of IgG antibodies was made by indirect immunofluorescence. RESULTS: The seropositive ratio fell in the 2-4 month group (15% seropositive) and increased between 5 months (47% seropositive) and 23 months (67%). Geometric mean titers (GMT) of the infants aged 2-4 months (GMT = 60) were statistically different (p < 0.0001, Student's t-test) to those from the group of pregnant women (GMT = 83) and those from the other infant groups (p < 0.001, least significant difference (LSD) test). The GMT of the groups between 5 and 23 months did not show significant differences whereas those of infants between 24 and 29 months (GMT = 179, 79% seropositive) were different from all the groups studied (p < 0.0001, LSD test). CONCLUSIONS: This study shows a significant association between the loss of passive HHV-7 antibody and age. HHV-7 enters the susceptible population at 5 months, leading to the high prevalence of antibodies between 24 and 29 months of age. This study also shows that natural infection by HHV-7 in children during their first years of life follows the infection pattern found in developing countries.

Discrepancies in viral gastroenteritis diagnosis: an unusual dual reovirus-adenovirus infection case.

BACKGROUND: A variable rate of false-positive results may be observed with commercial assays for the detection of rotavirus and adenovirus antigen in stool specimens, depending on the quality of the reagents and the presence of potentially interfering substances in stool samples. OBJECTIVE: The present report analyse the discrepant results that could be obtained by the commercially available diagnostic tests and that can mask the reliable viral diagnosis. STUDY DESIGN: One fecal sample was collected from a hospitalized child aged 6 months with acute watery diarrhea and dehydration. The fecal specimen was processed the same day for the rotavirus and adenovirus antigen detection. RESULTS: The sample was positive for rotavirus antigen by one-step membrane test based on immunochromatographic assays (ICA) and enzyme immunoassays (EIA) monoclonal test but it was negative by an EIA polyclonal test, polyacrylamide gel electrophoresis (PAGE) and RT-PCR assays. In the other hand, the sample was positive for adenovirus antigen by ICA and EIA adenovirus type 40/41. Finally, the sample showed by PAGE an electrophoretic profile resembled that of reovirus. CONCLUSION: The use of a wide repertory of diagnosis tests allowed to reach an unusual reovirus-adenovirus type 40/41 dual infection. This case also point out the potential participation of reovirus in the ethiology of the diarrhea illness.

Twenty year study of the occurrence of reovirus infection in hospitalized children with acute gastroenteritis in Argentina.

We studied the occurrence of reovirus infection in children hospitalized with acute gastroenteritis in Argentina during a 20-year interval (1981 through 2001). Three of 2854 (0.10%) stools were positive for reovirus but negative for adenovirus, astrovirus and rotavirus. Children infected with reovirus were <1 year old; one had meningoencephalitis in addition to gastroenteritis. This study indicates that reovirus is an uncommon cause of childhood gastroenteritis requires medical assistance.

Evidence of closely related picobirnavirus strains circulating in humans and pigs in Argentina.

BACKGROUND: On the basis of the published literature, it is still difficult to draw conclusions as to whether picobirnavirus (PBV) circulation is influenced by host species restriction. OBJECTIVE: To provide data regarding the genetic relatedness between porcine and human PBV strains present in Argentina as a means of defining the host range and epidemiology of these viruses. METHODS: Fecal specimens (n = 74) collected from kidney transplant patients (n = 55) and piglets (n = 19) were analyzed by RT-PCR using primers designed to amplify the porcine PBV genomic segment 2. Amplified sequences were further examined phylogenetically. RESULTS: By RT-PCR amplification 14 of 74 samples rendered amplicons of the expected 282 base pair size (8 detected from humans and 6 from pigs). Eleven amplicons (5 from humans and 6 from pigs) were selected for sequencing and subjected to phylogenetic analysis. The eleven amplicons revealed similarities between human and porcine viral sequences that ranged between 94.7 and 100% in identity. Phylogenetic analysis identified these 11 strains as PBV genogroup I-related strains and showed that they grouped as a single separate clade distinct from other PBV strains detected in humans and porcine from other countries. CONCLUSIONS: The present study suggests that closely related PBV strains infect both pigs and humans in Argentina and that the epidemiology of PBVs is not species restricted.

Genetic analysis of a novel human adenovirus with a serologically unique hexon and a recombinant fiber gene.

In February of 1996 a human adenovirus (formerly known as Ad-Cor-96-487) was isolated from the stool of an AIDS patient who presented with severe chronic diarrhea. To characterize this apparently novel pathogen of potential public health significance, the complete genome of this adenovirus was sequenced to elucidate its origin. Bioinformatic and phylogenetic analyses of this genome demonstrate that this virus, heretofore referred to as HAdV-D58, contains a novel hexon gene as well as a recombinant fiber gene. In addition, serological analysis demonstrated that HAdV-D58 has a different neutralization profile than all previously characterized HAdVs. Bootscan analysis of the HAdV-D58 fiber gene strongly suggests one recombination event.

Picobirnavirus causes persistent infection in pigs.

A study aimed to further understand the biology of porcine picobirnaviruses (PBV) was conducted between November 2003 and January 2008, on a farm located in the outskirts of Córdoba City, Argentina. PBV prevalence was examined by polyacrylamide gel electrophoresis and silver staining (PAGE S/S) on a total of 265 samples collected from pigs divided into four groups, according to age and physiological status. PBV detection rate was highest in the group of sows sampled within the lactogenic period (38.02%; p<0.05), followed by pregnant sows (15.09%), piglets aged 2-5 months of age (18.42%) and adult (> or =50 weeks) male pigs (0%). In addition, 103 samples collected in 3 follow-up studies were analyzed by PAGE S/S and reverse transcription followed by PCR (RT-PCR). Two of these studies followed female pigs from weaning up to slaughter and a third one from weaning up to 4 pregnancy periods. The results provide evidence that PBV establishes a persistent infection in the host with periods of silence intermingled with periods of low and high viral excretion. High PBV excretion levels were detected by PAGE S/S and were conditioned by age (primary infection) and host physiological status. Low PBV excretion levels were detected by RT-PCR throughout the entire study period. Sequence analysis of selected amplicons indicated that the virus excreted through the follow-up study was the same. These results suggest that porcine PBV is maintained in nature by transmission from infected asymptomatic individuals to susceptible ones.

Two instances of large genome profile picobirnavirus occurrence in Argentinian infants with diarrhea over a 26-year period (1977-2002).

BACKGROUND: Picobirnavirus' (PBV) association with diarrhea in children is not reliably established and the potential role of pathogenic PBV needs further investigations. OBJECTIVE: The aim of this study is to clarify the role of PBV in diarrhea illness in children. METHODS: Between January 1977 and December 2002, 2224 stool specimens were collected from children <3 years old with diarrhea illness. All samples were analyzed by the polyacrylamide gel electrophoresis technique (PAGE) for the presence of bisegmented dsRNA virus genomic pattern. Gels were dried and archived. This study procedure allowed us to keep a laboratory electrophoretic record of each sample assayed. In the present study, all the electrophoretic records were reviewed in order to identify PBV positive samples. RESULTS: Two out of 2224 (0.09%) stools were positive for large genome profile of PBV. These two positive samples were collected from hospitalized children <1 year old; one of them presenting rotavirus co-infection. CONCLUSIONS: The findings obtained in the present report support strong evidence that large genome profile PBV can be considered more an occasional viral agent rather than an etiological agent associated with diarrheal illness.

The epidemiology of acute viral gastroenteritis in hospitalized children in Cordoba city, Argentina: an insight of disease burden

Information concerning the disease burden of viral gastroenteritis has important implications for the use and monitoring the impact of public health policies. The present study, carried out in Córdoba city, Argentina, documents the epidemiology of severe viral diarrhea as well as the burden of viral gastrointestinal disease in the hospital children admission. A total of 133 stools were collected from hospitalized children (Town Childhood Hospital) suffering from acute diarrhea and studied for the presence of Group A rotavirus, astrovirus and adenovirus 40/41 by enzyme-immuno assay, between November 1997 and October 1998. Enteric viruses accounted for 42.1 percent of the total diarrheal cases analyzed. Group A rotaviruses, astroviruses, adenoviruses 40/41 and mixed infections were found in 35.3, 4.5, 1.5, and 0.8 percent studied specimens respectively. We estimated that 1 in 27 children in the 0-35 month-old cohort/range would be annually hospitalized for a viral gastroenteritis illness. The major impact on viral diarrhea lies on rotaviral infection, accouting for 84.0 percent of the viral diarrheal cases analyzed and for approximately one third of severe diarrheas requiring hospital admission in Córdoba City, Argentina

Agentes virales asociados al sindrome diarreico en pacientes trasplantados renales / Viral agents related to diarrheic syndrome in kidney transplanted patiens

El objetivo del presente estudio fue documentar la frequencia de agentes virales clásicos y emergentes y su asociación etiológica con el síndrome diarreico en pacientes transplantados renales en Córdoba, Argentina. Se estudiaron 42 muestras fecales de individuos transplantados renales, internados y ambulatórios, con o sin diarrea, todas obtenidas después del transplante. Los pacientes se encontraban bajo triple terapia inmunosupresora con esteroides, azatioprina y ciclosporina ó tacrolimus. Los resultados obtenidos revelaron la presencia de ratovirus grupo A y picobirnavirus en tres de nueve pacientes con síndrome diarreico severo (33.33 porciento), en ausencia de otros patógenos bacterianos entéricos. La presencia de estos agentes virales se correlacionó con niveles elevados de ciclosporina en sangue (> 290 ng/ml) o bien con un tratamiento inmunosupresor prolongado. En contraste, no se detectó ningún virus en la etiología de cuadros diarreicos severos en pacientes transplantados renales.

Agentes virales asociados al sindrome diarreico en pacientes trasplantados renales / Viral agents related to diarrheic syndrome in kidney transplanted patiens

El objetivo del presente estudio fue documentar la frequencia de agentes virales clásicos y emergentes y su asociación etiológica con el síndrome diarreico en pacientes transplantados renales en Córdoba, Argentina. Se estudiaron 42 muestras fecales de individuos transplantados renales, internados y ambulatórios, con o sin diarrea, todas obtenidas después del transplante. Los pacientes se encontraban bajo triple terapia inmunosupresora con esteroides, azatioprina y ciclosporina ó tacrolimus. Los resultados obtenidos revelaron la presencia de ratovirus grupo A y picobirnavirus en tres de nueve pacientes con síndrome diarreico severo (33.33 porciento), en ausencia de otros patógenos bacterianos entéricos. La presencia de estos agentes virales se correlacionó con niveles elevados de ciclosporina en sangue (> 290 ng/ml) o bien con un tratamiento inmunosupresor prolongado. En contraste, no se detectó ningún virus en la etiología de cuadros diarreicos severos en pacientes transplantados renales. (AU)