Human AdV Research Articles

A recombinant virus-like particle vaccine against adenovirus-7 induces a potent humoral response

Adenoviruses (AdVs) cause infections in humans that range from mild to severe, and can cause outbreaks particularly in close contact settings. Several human AdV types have been identified, which can cause a wide array of clinical manifestations. AdV types 4 and 7 (AdV-4 and AdV-7), which are among the most commonly circulating types in the United States, are known to cause acute respiratory disease that can result in hospitalization and rarely, death. Currently, the only vaccines approved for use in humans are live virus vaccines against AdV-4 and AdV-7, though these vaccines are only authorized for use in U.S. military personnel. While they are efficacious, use of these live virus vaccines carries considerable risks of vaccine-associated viral shedding and recombination. Here, we present an alternative vaccination strategy against AdV-7 using the virus-like particle platform (AdVLP-7). We describe the production of stable recombinant AdVLP-7, and demonstrate that AdVLP-7 is structurally analogous to wild-type AdV-7 virions (WT AdV-7). Preclinical immunogenicity studies in mice show that AdVLP-7 elicits a potent humoral immune response, comparable to that observed in mice immunized with WT AdV-7. Specifically, AdVLP-7 induces high titers of antibodies against AdV-7-specific antigens that can effectively neutralize AdV-7.

A Single Oral Immunization with a Replication-Competent Adenovirus-Vectored Vaccine Protects Mice from Influenza Respiratory Infection.

The development of effective and flexible vaccine platforms is a major public health challenge, especially in the context of influenza vaccines that have to be renewed every year. Adenoviruses (AdVs) are easy to produce and have a good safety and efficacy profile when administered orally, as demonstrated by the long-term use of oral AdV-4 and -7 vaccines in the U.S. military. These viruses therefore appear to be the ideal backbone for the development of oral replicating vector vaccines. However, research into these vaccines is limited by the ineffectiveness of human AdV replication in laboratory animals. The use of mouse AdV type 1 (MAV-1) in its natural host allows infection to be studied under replicating conditions. Here, we orally vaccinated mice with a MAV-1 vector expressing influenza hemagglutinin (HA) to assess the protection conferred against an intranasal challenge of influenza. We showed that a single oral immunization with this vaccine generates influenza-specific and -neutralizing antibodies and completely protects mice against clinical signs and viral replication, similar to traditional inactivated vaccines. IMPORTANCE Given the constant threat of pandemics and the need for annual vaccination against influenza and possibly emerging agents such as SARS-CoV-2, new types of vaccines that are easier to administer and therefore more widely accepted are a critical public health need. Here, using a relevant animal model, we have shown that replicative oral AdV vaccine vectors can help make vaccination against major respiratory diseases more available, better accepted, and therefore more effective. These results could be of major importance in the coming years in the fight against seasonal or emerging respiratory diseases such as COVID-19.

Detection of Protoparvovirus in wastewater and human adenovirus in a green leafy vegetable in an Environmental Education Center in southern Brazil

Abstract The presence of coliforms, Mastadenovirus (AdV), and Canine protoparvovirus (CPV) in an Environmental Education Center, which contains city kennel, was investigated. Surface water and wastewater, dogs’ stool, and lettuce samples were collected from the irrigation system in both periods October 2017 and February 2018. Water samples were analyzed for the presence of human AdV (HAdV) and canine AdV (CAV), CPV, total coliforms (TC), and Escherichia coli; lettuce for AdV; and dog stool for CAV and CPV. Sixty-seven samples were analyzed: dog stool (n = 33); water (n = 10), and root, stem, and leaf (n = 24) originated from eight lettuce samples. Coliforms and E. coli were tested by Colilert and viruses by PCR assays, respectively; and the amplicon was sequenced. E. coli, TC, and viruses were detected in both collections. Viruses were detected in 34.3% of samples, of which HAdV-C was present in 13% of water samples; HAdV-E in 8.7% (water and lettuce); CAV-1 in 13% (dog stool and water); CPV-2a in 56.5% (dog stool). Raccoon CPV-like and AdV not characterized were detected in one wastewater samples and one dog stool, respectively. To our knowledge, this is the first description of the presence of Raccoon CPV-like in water and HAdV-E in lettuce in Southern Brazil.

Genome Analyses of Ten New Ape Adenoviruses with Similarity to Human Mastadenovirus C.

The adenoviruses (AdVs) isolated from humans are taxonomically grouped in seven different species in the Mastadenovirus genus (HAdV-A through G). AdVs isolated from apes are often included in one of the human AdV species. Here we describe the sequence analyses of ten new AdVs that are related to the HAdV-C species and that were isolated from healthy western lowland gorillas, bonobos, chimpanzees, and orangutans kept in Dutch zoos. We analyzed these viruses and compared their genome sequences to those of human- and ape-derived AdV sequences in the NCBI GenBank database. Our data demonstrated that the ape-derived viruses clustering to HAdV-C are markedly distinct from the human HAdV-C species in the size and nucleotide composition (%GC) of their genome, differ in the amino-acid sequence of AdV proteins, and have longer RGD-loops in their penton-base proteins. The viruses form three well-separated clades (the human, the gorilla, and the combined group of the bonobo and chimpanzee viruses), and we propose that these should each be given species-level ranks. The Ad-lumc005 AdV isolated from orangutans was found to be very similar to the gorilla AdVs, and bootstrap inference provided evidence of recombination between the orangutan AdV and the gorilla AdVs. This suggests that this virus may not be a genuine orangutan AdV but may have been transferred from a gorilla to an orangutan host.

Adenovirus in fishery harbours and identification of contamination sources

Adenoviruses (AdVs) are a major cause of clinical infections and have been proposed as indicators of water quality. However, quantitative data on the environmental prevalence of AdVs is lacking. We investigated the prevalence, distribution, seasonal occurrence, quantity, and genotype of AdVs in 13 fishing harbours in Taiwan. AdVs in the water samples were isolated by membrane filtration and the AdV DNA was extracted. Next, AdVs were detected using nested polymerase chain reaction. Genotyping and phylogenetic analysis were performed to identify various AdV genotypes present in the water samples. The F species human AdV (HAdV) serotype 41 (63.6%) and C species porcine AdV (PAdV) serotype 5 (33.3%) were more prevalent than the other serotypes. The prevalence of AdVs was highest in the fall, followed by in the spring and summer. Among the fishing harbours, the highest detection rate of AdVs was observed in Yenpudongang in all seasons. However, Puoziliao was the only site at which AdVs were not detected during the study period. AdV detection at sampling sites may be correlated with sewage and livestock wastewater discharge via outflow of nearby rivers to fishing ports. Statistical analysis (Mann–Whitney U test) based on data from water quality indicators revealed that the presence of AdVs was significantly associated with the heterotrophic plate count, pH, and salinity. Human and swine population data from nearby local townships and river/drainage basins were collected from the Taiwan Central Government's website. The data were analyzed using Spearman's rank correlation coefficient to determine the relationship between the prevalence of AdVs, HAdVs, and PAdVs in fishing harbours, and microbial water quality indicators. Statistical evidence indicated that the detection levels of HAdVs and PAdVs in fishing harbours were mainly associated with human and swine populations in the corresponding river/drainage basin, respectively. Additionally, the swine population in the river/drainage basin was positively correlated with microbial water quality indicators.

The FDA-Approved Drug Nelfinavir Inhibits Lytic Cell-Free but Not Cell-Associated Nonlytic Transmission of Human Adenovirus.

Adenoviruses (AdVs) are prevalent and give rise to chronic and recurrent disease. Human AdV (HAdV) species B and C, such as HAdV-C2, -C5, and -B14, cause respiratory disease and constitute a health threat for immunocompromised individuals. HAdV-Cs are well known for lysing cells owing to the E3 CR1-β-encoded adenovirus death protein (ADP). We previously reported a high-throughput image-based screening framework and identified an inhibitor of HAdV-C2 multiround infection, nelfinavir mesylate. Nelfinavir is the active ingredient of Viracept, an FDA-approved inhibitor of human immunodeficiency virus (HIV) aspartyl protease that is used to treat AIDS. It is not effective against single-round HAdV infections. Here, we show that nelfinavir inhibits lytic cell-free transmission of HAdV, indicated by the suppression of comet-shaped infection foci in cell culture. Comet-shaped foci occur upon convection-based transmission of cell-free viral particles from an infected cell to neighboring uninfected cells. HAdV lacking ADP was insensitive to nelfinavir but gave rise to comet-shaped foci, indicating that ADP enhances but is not required for cell lysis. This was supported by the notion that HAdV-B14 and -B14p1 lacking ADP were highly sensitive to nelfinavir, although HAdV-A31, -B3, -B7, -B11, -B16, -B21, -D8, -D30, and -D37 were less sensitive. Conspicuously, nelfinavir uncovered slow-growing round HAdV-C2 foci, independent of neutralizing antibodies in the medium, indicative of nonlytic cell-to-cell transmission. Our study demonstrates the repurposing potential of nelfinavir with postexposure efficacy against different HAdVs and describes an alternative nonlytic cell-to-cell transmission mode of HAdV.

Two ICD Inducers are better than one for induction of anti-tumor immunity in cold carcinomas

Abstract Background Cytotoxic agents and viruses cause Immunogenic Cell Death (ICD), which initiates a primary immune response in tumor-bearing hosts by releasing cellular antigens with immune chaperones. We postulate that two ICD inducers are better than one in immune competent mouse models of colorectal and breast cancer. Methods Approximately 6 mm diameter CT26 rectal or 4T1 breast carcinomas were established in groups of 5–7 BALB/c mice and injected once intratumorally (IT) with oxaliplatin (OX) mixed with a human adenovirus AdV optimized for calreticulin externalization in 3-D spheroids of human carcinomas. Tumor volumes were measured every other day and rate of growth analyzed by Rate-Based T/C Ratio at 19–21 days. Tumor-Infiltrating Lymphocytes (TIL) and nodal cytotoxicity were assessed 11 days after treatment. Results In 3 experiments with OX-AdV IT in PBS buffer the T/C ratios were 0.17–0.29 those of the volume of PBS IT injected mice. The T/C Ratio for OX-AdV IT in D5W (used to stabilize the OX) was 0.10 of the IT control volume with 0.32–0.40 for OX or AdV alone and with all groups different by P<0.05 by 2-way ANOVA. OX-AdV IT increased TIL by 4-fold and decreased CD8+PD-1+EOMES+ from 79% to 19% with a dramatic influx of CD8+PD-1-Eomes- T cells compared to PBS IT controls. Draining node lymphocytes were cytotoxic to CT26 cells from OX-AdV IT mice while lymphocytes from PBS IT mice were not. OX-AdV IT in D5W caused 40% of mice to be complete responders that later rejected a contralateral challenge of CT26. Conclusions The buffer for IT treatment with OX is critical. The two ICD inducer formulation with D5W is promising as a checkpoint therapy sensitizer for carcinomas that lack TIL or resist checkpoint inhibitor therapy like colorectal carcinoma.

Seasonal difference of human adenoviruses in a subtropical river basin based on 1-year monthly survey.

In this study, the seasonal difference and the observable presence/absence of human adenovirus (HAdV) in the Puzih River basin in Taiwan was investigated. A total of 288 water samples were collected from 24 sites from March 2014 to February 2015. Human AdV analysis of sample was subjected to viral concentration using a GN-6 Metricel® filter, followed by DNA extraction, nested-PCR, and qPCR. Human AdV was detected in 34.3 % (99/288) of the entire river water sample. A higher percentage of HAdV (76.4 %) was obtained during the winter. The HAdV median concentration was relatively high in fall (1.4 × 10(3) copies/L) and winter (2.8 × 10(3) copies/L). Significant difference and correlation were found between the seasonal variation of HAdV and water quality parameters, including heterotrophic plate count, total coliform, water temperature, and turbidity. The most frequently identified HAdV (subgenus F) serotype was 41. Human AdV-41 is the main cause of gastroenteritis and should be considered for associated human health risk potential in the Puzih River basin.

Taxonomy proposal for Old World monkey adenoviruses: characterisation of several non-human, non-ape primate adenovirus lineages.

A species classification regarding Old World monkey adenoviruses is proposed. We determined the nucleotide sequences of PCR-amplified fragments from the genes of the IVa2, DNA-dependent DNA polymerase, penton base, and hexon proteins from every simian adenovirus (SAdV) serotype that originated from Old World monkeys for which the full genome sequence had not yet been published. We confirmed that the majority of Old Word monkey SAdVs belong to two previously established species. Interestingly, one is the most recently established human AdV species, Human mastadenovirus G, which includes a single human virus, HAdV-52, as well as SAdV-1, -2, -7, -11, -12, and -15. The other approved species, Simian mastadenovirus A includes SAdV-3, -4, -6, -9, -10, -14, and -48. Several SAdVs (SAdV-5, -8, -49, -50) together with baboon AdV-1 and rhesus monkey AdV strains A1139, A1163, A1173, A1258, A1285, A1296, A1312, A1327 and A1335 have been proposed to be classified into an additional species, Simian mastadenovirus B. Another proposed species, Simian mastadenovirus C has been described for SAdV-19, baboon AdV-2/4 and -3. Our study revealed the existence of four additional AdV lineages. The corresponding new candidate species are Simian mastadenovirus D (for SAdV-13), Simian mastadenovirus E (for SAdV-16), Simian mastadenovirus F (for SAdV-17 and -18), and Simian mastadenovirus G (for SAdV-20). Several biological and genomic properties, such as the host origin, haemagglutination profile, number of fibre genes, and G+C content of the genome, strongly support this classification. Three SAdV strains originating from the American Type Culture Collection turned out to be mixtures of at least two virus types, either of the same species (SAdV-12 and -15 types from Human mastadenovirus G) or of two different species (SAdV-5 types from Simian mastadenovirus B and Human mastadenovirus G).

The Intracellular Domain of the Coxsackievirus and Adenovirus Receptor Differentially Influences Adenovirus Entry.

The coxsackievirus and adenovirus receptor (CAR) is a cell adhesion molecule used as a docking molecule by some adenoviruses (AdVs) and group B coxsackieviruses. We previously proposed that the preferential transduction of neurons by canine adenovirus type 2 (CAV-2) is due to CAR-mediated internalization. Our proposed pathway of CAV-2 entry is in contrast to that of human AdV type 5 (HAdV-C5) in nonneuronal cells, where internalization is mediated by auxiliary receptors such as integrins. We therefore asked if in fibroblast-like cells the intracellular domain (ICD) of CAR plays a role in the internalization of the CAV-2 fiber knob (FK(CAV)), CAV-2, or HAdV-C5 when the capsid cannot engage integrins. Here, we show that in fibroblast-like cells, the CAR ICD is needed for FK(CAV) entry and efficient CAV-2 transduction but dispensable for HAdV-C5 and an HAdV-C5 capsid lacking the RGD sequence (an integrin-interacting motif) in the penton. Moreover, the deletion of the CAR ICD further impacts CAV-2 intracellular trafficking, highlighting the crucial role of CAR in CAV-2 intracellular dynamics. These data demonstrate that the CAR ICD contains sequences important for the recruitment of the endocytic machinery that differentially influences AdV cell entry. Understanding how viruses interact with the host cell surface and reach the intracellular space is of crucial importance for applied and fundamental virology. Here, we compare the role of a cell adhesion molecule (CAR) in the internalization of adenoviruses that naturally infect humans and Canidae. We show that the intracellular domain of CAR differentially regulates AdV entry and trafficking. Our study highlights the mechanistic differences that a receptor can have for two viruses from the same family.

Animal and human enteric viruses in water and sediment samples from dairy farms

The detection of enteric viruses accompanied by a characterization of the viruses found in a given environmental matrix may inform about the sources of fecal contamination. In the present work, 55 water samples and 20 sediment samples were collected from 21 small farms in southern Brazil. Coliform counting was done as well as molecular detection of human enterovirus (EV), and human and animal adenoviruses. Viral detection was performed using real-time quantitative PCR (qPCR). Furthermore, the viral viability of human AdV (HAdV) by ICC-RT-qPCR in sediment and water samples was analyzed. Regarding to the coliforms, only 72.7% of the samples showed fecal contamination. HAdV was detected in 87.3% of water samples, followed by AvAdV (27.3%), CAV (20%), BAV (7.3%) and PoAdV or EV (1.8%). From the sediment samples, HAdV (80%) followed by CAV (20%), BAV (5%) and no positive results for PoAdV or EV. The viral loads ranged from 1.57×102gc/L up to 6.68×109gc/L (water), and from 1.97×103gc/g to 2.18×108gc/g (sediment). Most of these viral particles in water should be non-infectious, since after the ICC-PCR, HAdV was detected in only 4 samples (8.8%). On the other hand, it is noticeable that 5 sediment samples (25%) gave positive results for the presence of infectious viral particles.

Prevalence, quantification, and typing of human adenoviruses detected in river water in Taiwan.

The prevalence of human adenoviruses (HAdV) in river waters was investigated in this study. Water samples were collected from 13 rivers in Taiwan, concentrated, and assessed for the presence of HAdVs using nested polymerase chain reaction (PCR). Human AdV positive samples were then subjected to real-time PCR (qPCR) to quantify the viral genomes and further subjected to primer-based genotyping to identify the various serotypes present. For each water sample, several water quality parameters were evaluated, including heterotrophic plate count, total coliform, Escherichia coli, water temperature, pH, conductivity, and dissolved oxygen. Among the 13 rivers examined, four rivers (30.8%) were found to contain HAdVs. The major genotype was F species HAdV serotype 41. The mean HAdVs concentrations ranged from 6.10 × 10(2) to 8.51 × 10(2)copies/L. No significant differences were observed between the presence of HAdVs, and all of the water quality parameters evaluated (heterotrophic plate count, total coliform, E. coli, water temperature, pH, conductivity, and dissolved oxygen). Given the potential health risks posed by the presence of enteric viruses in environmental waters, further assessment is desirable with respect to possible sources, virus transport, and survival of viruses in the aquatic environment.

The genome sequence of a novel simian adenovirus in a chimpanzee reveals a close relationship to human adenoviruses

Recently, several reports have revealed that some simian adenoviruses (AdVs) strains show a close relationship to human AdVs. In the present study, a simian AdV strain named SAdV-ch1 was detected in chimpanzees in China, and its complete genome was determined. Phylogenetic analysis revealed SAdV-ch1 clustering in a clade that was separate from all of the other simian AdVs but genetically close to a human AdV strain, HAdV-18 (GenBank no. GU191019), sharing 92.5 % sequence identity with it. Recombination analysis provided evidence that a recombination event had occurred between SAdV-ch1 and HAdV-61 (JF964962), where SAdV-ch1 exchanged partial of its hexon gene segment with HAdV-61, leading to the recombinant HAdV-31 (AM749299).

A retrospective performance evaluation of an adenovirus real‐time PCR assay

Human adenoviruses (AdVs) cause a wide range of diseases. To date, there are at least 60 known human AdV types and, as these exhibit high levels of genetic variation this could impact potentially upon their detection by polymerase chain reaction (PCR)-based technology. Here, the sensitivity of a pan-AdV real-time PCR assay (AdV-PCR) used widely for testing clinical samples was determined retrospectively. An in silico analysis was performed initially using the 370 AdV sequences available on the Genbank database. To investigate for potential false-negative results, two additional AdV-PCR assays were used to re-evaluate 779 respiratory samples submitted for virus testing and 1,012 nasal swab samples collected as part of an ongoing community-based study. The results were then compared to those obtained by AdV-PCR. In silico analysis showed the presence of mismatches in the AdV-PCR primers and probe for most AdV sequences available on Genbank. Notably, 215 of the 370 (58%) sequences had at least three mismatches with the AdV-PCR forward primer. Of the 779 clinical samples, 88 were identified as AdV-positive, of which 84 were positive by the AdV-PCR. The four samples providing false-negative results in the AdV-PCR had high cycle threshold values in the other methods suggesting that sampling at low load, rather than sequence variation, was responsible for the negative results. No false-negative AdV-PCR results were observed for the community-based study samples. Reassuringly, the results show that despite the high level of sequence variation in the AdV-PCR assay oligonucleotide targets, the assay remains suitable for routine detection of human AdV strains.

Deep RNA Sequencing Reveals Complex Transcriptional Landscape of a Bat Adenovirus

Bat adenoviruses are a group of recently identified adenoviruses (AdVs) which are highly prevalent in bats yet share low similarity to known AdVs from other species. In this study, deep RNA sequencing was used to analyze the transcriptome at five time points following the infection of a bat AdV in a kidney cell line derived from a myotis bat species. Evidence of AdV replication was observed with the proportion of viral RNAs ranging from 0.01% at 6 h to 1.3% at 18 h. Further analysis of viral temporal gene expression revealed three replication stages, the early-stage genes encoding mainly host interaction proteins, the intermediate-stage genes for the DNA replication and assembly proteins, and the late-stage genes for most structural proteins. Several bat AdV genes were expressed at stages that differed from those of their counterpart genes previously reported for human AdV type 2. In addition, single-base resolution splice sites of several genes and promoter regions of all 30 viral genes were fully determined. Simultaneously, the temporal cellular gene expression profiles were identified. The most overrepresented functional categories of the differentially expressed genes were related to cellular immune response, transcription, translation, and DNA replication and repair. Taken together, the deep RNA sequencing provided a global, transcriptional profile of the novel bat AdV and the virus-host interactions which will be useful for the understanding and investigation of AdV replication, pathogenesis, and specific virus-bat interactions in future research.

Novel Adenoviruses in Wild Primates: a High Level of Genetic Diversity and Evidence of Zoonotic Transmissions

Adenoviruses (AdVs) broadly infect vertebrate hosts, including a variety of nonhuman primates (NHPs). In the present study, we identified AdVs in NHPs living in their natural habitats, and through the combination of phylogenetic analyses and information on the habitats and epidemiological settings, we detected possible horizontal transmission events between NHPs and humans. Wild NHPs were analyzed with a pan-primate AdV-specific PCR using a degenerate nested primer set that targets the highly conserved adenovirus DNA polymerase gene. A plethora of novel AdV sequences were identified, representing at least 45 distinct AdVs. From the AdV-positive individuals, 29 nearly complete hexon genes were amplified and, based on phylogenetic analysis, tentatively allocated to all known human AdV species (Human adenovirus A to Human adenovirus G [HAdV-A to -G]) as well as to the only simian AdV species (Simian adenovirus A [SAdV-A]). Interestingly, five of the AdVs detected in great apes grouped into the HAdV-A, HAdV-D, HAdV-F, or SAdV-A clade. Furthermore, we report the first detection of AdVs in New World monkeys, clustering at the base of the primate AdV evolutionary tree. Most notably, six chimpanzee AdVs of species HAdV-A to HAdV-F revealed a remarkably close relationship to human AdVs, possibly indicating recent interspecies transmission events.

Molecular characterization of adenovirus from clinical samples through analysis of the hexon and fiber genes

Human adenoviruses (HAdVs) are common pathogens associated with a variety of clinical manifestations. Although most infections are self-limiting, HAdVs can cause severe or lethal infections in immunocompromised as well as in healthy individuals. Several HAdVs have recently been characterized as emerging pathogens. In Italy, epidemiological, and especially molecular epidemiological, information on this pathogen is scarce. This study describes the characterization by cell culture, PCR and phylogenetic analysis of HAdV strains originating from a small collection of clinical samples gathered between 2008 and 2009. The distribution of different HAdV species was studied and the possible presence of newly emerging types was ascertained. A broad-range primer pair was used, targeting a portion of the hexon gene, in combination with species-specific primer pairs targeting a portion of the fiber gene. Human and animal reference AdV strains were included in the study. The broad-range assay identified all HAdV strains (study and reference samples), as well as three out of four animal AdV reference strains. Seven different types belonging to three HAdV species (B, C and F) were identified in the study samples. Species C was by far the most frequent. Two co-infections were detected, each with two serotypes within species C (types 1/2 and 2/6). The combined use of these two PCR assays--allowing not only the identification of known types but also, potentially, the discovery of newly emerging ones--can provide valuable epidemiological information on the spread of HAdVs.

Molecular identification of adenovirus causing respiratory tract infection in pediatric patients at the University of Malaya Medical Center

BackgroundThere are at least 51 adenovirus serotypes (AdV) known to cause human infections. The prevalence of the different human AdV (HAdV) serotypes varies among different regions. Presently, there are no reports of the prevalent HAdV types found in Malaysia. The present study was undertaken to identify the HAdV types associated primarily with respiratory tract infections (RTI) of young children in Malaysia.MethodsArchived HAdV isolates from pediatric patients with RTI seen at the University of Malaya Medical Center (UMMC), Kuala Lumpur, Malaysia from 1999 to 2005 were used. Virus isolates were inoculated into cell culture and DNA was extracted when cells showed significant cytopathic effects. AdV partial hexon gene was amplified and the sequences together with other known HAdV hexon gene sequences were used to build phylogenetic trees. Identification of HAdV types found among young children in Malaysia was inferred from the phylograms.ResultsAt least 2,583 pediatric patients with RTI sought consultation and treatment at the UMMC from 1999 to 2005. Among these patients, 48 (< 2%) were positive for HAdV infections. Twenty-seven isolates were recovered and used for the present study. Nineteen of the 27 (~70%) isolates belonged to HAdV species C (HAdV-C) and six (~22%) were of HAdV species B (HAdV-B). Among the HAdV-C species, 14 (~74%) of them were identified as HAdV type 1 (HAdV-1) and HAdV type 2 (HAdV-2), and among the HAdV-B species, HAdV type 3 (HAdV-3) was the most common serotype identified. HAdV-C species also was isolated from throat and rectal swabs of children with hand, foot, and mouth disease (HFMD). Two isolates were identified as corresponding to HAdV-F species from a child with HFMD and a patient with intestinal obstruction.ConclusionsHAdV-1 and HAdV-2 were the most common HAdV isolated from pediatric patients who sought treatment for RTI at the UMMC from 1999 to 2005. HAdV-B, mainly HAdV-3, was recovered from ~22% of the patients. These findings provide a benchmark for future studies on the prevalence and epidemiology of HAdV types in Malaysia and in the region.

Single-strand conformation polymorphism analysis for the study of adenoviral diversity in urban rivers

The diversity of human adenoviruses (AdVs) in river waters was studied by single-strand conformational polymorphism (SSCP) analysis. Water samples were collected between 2002 and 2003 from 4 rivers in the Gyeonggi Province, South Korea. Forty-six (79.3%) of the 58 samples were positive for AdVs as determined on PCR amplification. Nine different SSCP profiles (profiles A to I) were detected in all the AdVs-positive samples by SSCP analysis, and most of the AdVs-positive samples (38 of 46 samples; 82.6%) showed the SSCP profile D. Nine different sequences were obtained in the SSCP profiles; sequence alignments and phylogenetic analysis identified 5 different sequences that were closely related to the human AdV type 41, and the 4 different sequences that were closely related to human AdV types 3, 4, 12, and 40. Two AdVs genomic variants were detected (types 3 and 41 in A, types 12 and 41 in B, and 2 genomic variants of type 41 in C) in SSCP profiles A, B, and C, respectively. SSCP analysis could be a useful technique for the identification of genetic variants of AdVs and for studying AdVs diversity in urban rivers.

A Framework for Analyzing the Impact of International Students on Economic Development

In the modern era of knowledge-based economies, the sustainability of long-run economic growth is inextricably linked to the availability of high quality human capital. This is particularly critical, especially for certain regions within industrialized countries, such as the United States and Canada, that are facing population declines and, by extension, looming labor shortages. Attracting foreigners is one way of dealing with the impending shortage of human capital for some jurisdictions. Individuals, especially those who are relatively young, can move from one country to another as temporary workers, migrants, or as international students. Federal, provincial, and state governments are currently reviewing their employment, immigration, and education policies to ensure that they are properly designed to attract migrants and help meet the challenge of a shrinking labor force. This study highlights the emergence of knowledge-based economies, migration patterns of international students, and the resulting birth of the phenomenon of brain circulation. New long-run growth theories explain why these developments are dependent on an educated workforce and, have in fact, created a global market for international students. New growth theorists assert that technology and human capital as factors of production are unique in that there is the potential for producing increasing rather than diminishing marginal returns. An educated labor force (human Int Adv Econ Res (2010) 16:126–127 DOI 10.1007/s11294-009-9240-9