A Zoonotic Adenoviral Human Pathogen Emerged through Genomic Recombination among Human and Nonhuman Simian Hosts.

Genomics analysis of a historically intriguing and predicted emergent human adenovirus (HAdV) pathogen, which caused pneumonia and death, provides insight into a novel molecular evolution pathway involving "ping-pong" zoonosis and anthroponosis. The genome of this promiscuous pathogen is embedded with evidence of unprecedented multiple, multidirectional, stable, and reciprocal cross-species infections of hosts from three species (human, chimpanzee, and bonobo). This recombinant genome, typed as HAdV-B76, is identical to two recently reported simian AdV (SAdV) genomes isolated from chimpanzees and bonobos. Additionally, the presence of a critical adenoviral replication element found in HAdV genomes, in addition to genes that are highly similar to counterparts in other HAdVs, reinforces its potential as a human pathogen. Reservoirs in nonhuman hosts may explain periods of apparent absence and then reemergence of human adenoviral pathogens, as well as present pathways for the genesis of those thought to be newly emergent. The nature of the HAdV-D76 genome has implications for the use of SAdVs as gene delivery vectors in human gene therapy and vaccines, selected to avoid preexisting and potentially fatal host immune responses to HAdV.IMPORTANCE An emergent adenoviral human pathogen, HAdV-B76, associated with a fatality in 1965, shows a remarkable degree of genome identity with two recently isolated simian adenoviruses that contain cross-species genome recombination events from three hosts: human, chimpanzee, and bonobo. Zoonosis (nonhuman-to-human transmission) and anthroponosis (human to nonhuman transmission) may play significant roles in the emergence of human adenoviral pathogens.

Hawaii state legislator views on e-cigarettes and likelihood of legislative action.

OBJECTIVE: To examine perspectives on e-cigarette use and regulations in Hawaii through key informant interviews with state legislators. BACKGROUND: E-cigarette use is rapidly increasing, with sales in 2013 topping $1 billion in the United States, but e-cigarettes are still a largely unregulated industry. Although e-cigarettes are thought by most to be a healthier alternative to traditional cigarettes, long-term health effects are not yet known. METHODS: Semistructured key informant interviews were conducted with Hawaii state legislators (n = 15). RESULTS: We found a lack of consensus among legislators, which suggests that substantial legislative action is unlikely in the upcoming session. However, most legislators believe that some type of incremental legislation will pass, such as enactment of a small tax, limitations on advertising to protect adolescents, or regulations concerning where people can use e-cigarettes. CONCLUSION: Legislators eagerly await further research to clarify the overall benefits and harms of e-cigarettes at both the individual and population levels.

Describing the Medical Needs of Hawai'i's Houseless Population During COVID at Free Student Run Outpatient Clinics (Hawai'i HOME Project).

Hawai'i experiences some of the highest rates of houselessness per capita in the country. COVID-19 has exacerbated these disparities and made it difficult for these individuals to seek medical care. Hawai'i's Houseless Outreach in Medical Education (HOME) clinic is the largest student run free clinic in the state, which provides medical services to this patient population. This article reports the demographics, medical needs, and services provided to patients of Hawai'i's HOME clinic during the era of COVID-19. From September 2020 to 2021, the HOME clinic saw 1198 unique visits with 526 distinct patients. The most common chief complaints included wound care (42.4%), pain (26.9%), and skin complaints (15.7%). A large portion of the population suffered from comorbidities including elevated blood pressure (66%), a formal reported history of hypertension (30.6%), diabetes (11.6%), and psychiatric concerns including schizophrenia (5.2%) and generalized anxiety (5.1%). Additionally, a large portion of patients (57.2%) were substance users including 17.8% of patients endorsing use of alcohol, 48.5% tobacco and 12.5% marijuana. The most common services provided were dispensation of medication (58.7%), wound cleaning/dressing changes (30.7%), and alcohol or other drug cessation counseling (25.2%). This study emphasizes that the houseless are a diverse population with complex, evolving medical needs and a high prevalence of chronic diseases and comorbidities.

Five genome sequences of subspecies B1 human adenoviruses associated with acute respiratory disease.

Five genomes of human subspecies B1 adenoviruses isolated from cases of acute respiratory disease have been sequenced and archived for reference. These include representatives of two prevalent genomic variants of HAdV-7, i.e., HAdV-7h and HAdV-7d2. The other three are HAdV-3/16, HAdV-16 strain E26, and HAdV-3+7 strain Takeuchi. All are recombinant genomes. Genomics and bioinformatics provide detailed views into the genetic makeup of these pathogens and insight into their molecular evolution. Retrospective characterization of particularly problematic older pathogens such as HAdV-7h (1987) and intriguing isolates such as HAdV-3+7 strain Takeuchi (1958) may provide clues to their phenotypes and serology and may suggest protocols for prevention and treatment.

Complete genome sequence of human adenovirus prototype 17.

As one of the first five human adenoviruses (HAdVs) to be sequenced, type 17 was important as a reference tool for comparative genomics of recently isolated HAdV pathogens in species D. HAdV-D17 was the first species D adenovirus to be sequenced and was deposited in GenBank in 1999. These genome data were not of high quality, and a redetermination of the same stock virus provides corrected data; among the differences are a length of 35,139 bp versus 35,100 bp in the original, and 160 mismatches to the original genome were found. Annotation of the coding sequences reveals 39 as opposed to 8, a finding which is important for phylogenomic studies.

Computational analysis of two species C human adenoviruses provides evidence of a novel virus.

Human adenovirus C (HAdV-C) species are a common cause of respiratory infections and can occasionally produce severe clinical manifestations. A deeper understanding of the variation and evolution in species HAdV-C is especially important since these viruses, including HAdV-C6, are used as gene delivery vectors for human gene therapy and in other biotechnological applications. Here, the full-genome analysis of the prototype HAdV-C6 and a recently identified virus provisionally termed HAdV-C57 are reported. Although the genomes of all species HAdV-C members are very similar to each other, the E3 region, hexon and fiber (ten proteins total) present a wide range of identity values at the amino acid level. Studies of these viruses in comparison to the other three HAdV-C prototypes (1, 2, and 5) comprise a comprehensive analysis of the diversity and conservation within HAdV-C species. HAdV-C6 contains a recombination event within the constant region of the hexon gene. HAdV-C57 is a recombinant virus with a fiber gene nearly identical to HAdV-C6 and a unique hexon distinguished by its loop 2 motif.

Effect of Hometown Seasonality on Undergraduate Students' Risk of Developing Seasonal Affective Disorder.

Seasonal affective disorder (SAD) is a prevalent and potentially serious medical condition. Young adults are at particularly high risk. However, it is unknown if college students whose hometowns are in geographic areas with less seasonal variability, such as in the state of Hawai'i, are particularly vulnerable if they attend schools in areas with seasonal variability. An adapted version of the Seasonal Patterns Assessment Questionnaire (SPAQ) was administered to students at 3 universities to test this hypothesis. Surveys were administered twice: a baseline (T0) assessment in the fall and a follow-up (T1) assessment in the winter and were administered in the second month of each semester. A linear regression model was constructed to identify potential risk factors for developing seasonal fluctuations in mood (SPAQ scores T1-T0). Study subjects (n=115) from non-seasonal hometowns had a 1.6-point greater increase in SPAQ score than students from seasonal hometowns (-0.26 ± 3.88 vs 1.35 ± 3.03; P =.01). This difference is independent of demographic and lifestyle predictors (linear regression coefficient: ß = 1.73; standard error = 0.68; P =.012). Interestingly, SPAQ score changes of students from seasonal hometowns did not differ significantly from 0 (t = -0.97; P =.33), indicating that they did not generally experience seasonal shifts in depressive symptoms. Students from less seasonal hometowns and counselors at seasonal institutions should be aware that these students could be more at risk of developing depressive symptoms and address these concerns before interfering with students' daily and academic lives.

Computational analysis identifies human adenovirus type 55 as a re-emergent acute respiratory disease pathogen.

Novel human adenoviruses (HAdVs) arise from genome recombination. Analysis of HAdV type 55 from an outbreak in China shows a hexon recombination between HAdV-B11 and HAdV-B14, resulting in a genome that is 97.4% HAdV-B14. Sporadic appearances as a re-emergent pathogen and misidentification as "HAdV-B11a" are due to this partial hexon.

Genomic and bioinformatics analyses of HAdV-14p, reference strain of a re-emerging respiratory pathogen and analysis of B1/B2.

Unlike other human adenovirus (HAdV) species, B is divided into subspecies B1 and B2. Originally this was partly based on restriction enzyme (RE) analysis. B1 members, except HAdV-50, are commonly associated with respiratory diseases while B2 members are rarely associated with reported respiratory diseases. Recently two members of B2 have been identified in outbreaks of acute respiratory disease (ARD). One, HAdV-14, has re-emerged after an apparent 52-year absence. Genomic analysis and bioinformatics data are reported for HAdV-14 prototype for use as a reference and to understand and counter its re-emergence. The data complement and extend the original criteria for subspecies designation, unique amongst the adenoviruses, and highlight differences between B1 and B2, representing the first comprehensive analysis of this division. These data also provide finer granularity into the pathoepidemiology of the HAdVs. Whole genome analysis uncovers heterogeneous identity structures of the hexon and fiber genes amongst the HAdV-14 and the B1/B2 subspecies, which may be important in prescient vaccine development. Analysis of cell surface proteins provides insight into HAdV-14 tropism, accounting for its role as a respiratory pathogen. This HAdV-14 prototype genome is also a reference for applications of B2 adenoviruses as vectors for vaccine development and gene therapy.

Examining the Association Between Different Aspects of Socioeconomic Status, Race, and Disability in Hawaii.

Socioeconomic status and race/ethnicity are known to be associated with health disparities. This study used data (2010-2014) from the American Community Survey. Respondents over age 30 from Hawaii were included (n = 44,921). Outcome variables were self-reported disability in vision, hearing, ambulatory function, self-care, independent living, or cognitive function. Four measures of socioeconomic status were personal income, average income for the area, income inequality for area, and education. This study used multivariable logistic regression to predict disability by race/ethnicity and socioeconomic status, controlling for age and gender. All four measures of socioeconomic status were significant predictors of at least one type of disability after adjustment for age, gender, and other measures of socioeconomic status. Higher education was significantly related to having every type of disability. Similarly, people with high personal income were less likely to have each type of disability than those with middle income, and those with low income were more likely to have all disabilities except hearing. Income inequality was significantly associated with half the disabilities. Low area income was significantly associated with increased vision-related disability, while high income was associated with less likelihood of hearing-related disability. Native Hawaiians were significantly more likely to report having a disability than Filipinos and Chinese for all six types of disability, Japanese for four, and whites for two, after adjustment. These results suggest that in order to reduce health disparities for Native Hawaiians, as well as other ethnic groups, a range of socioeconomic factors need to be addressed.

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.

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.

E-cigarette Use Related to Demographic Factors in Hawai'i.

E-cigarette use is rapidly expanding in the United States and is projected to be a $3 billion industry by the end of this year. E-cigarette use in Hawai'i is significantly higher than national averages. The goal of this study was to examine the relationship in Hawai'i between demographic characteristics and several aspects of e-cigarette use including percentage of residents trying e-cigarettes, reasons for use, and perceived effects on health. Survey data were collected from a random sample of Hawai'i residents via the telephone in the summer of 2015, using methodology similar to that of the Hawai'i Health Survey. Chi-squared tests found e-cigarette use to be significantly associated with age (P =.001), gender (P =.03), ethnicity (P <.001), and education (P <.001). Among e-cigarette users, 12% said they started smoking regular cigarettes after starting e-cigarettes, 21% said their use of regular cigarettes did not change, 6% said they reduced use of regular cigarettes, and 20% said they completely stopped smoking regular cigarettes. Multivariable logistic regression results suggest Native Hawaiians (OR=29.1, P =.01) and Filipinos (OR=24.3, P =.01) were significantly more likely to report perceived improved health due to e-cigarette use compared to Caucasians. Given existing health disparities for Native Hawaiians and Filipinos, the fact that these groups are significantly more likely than other ethnic/racial groups to report that e-cigarettes improved their health bears notice and highlights the need for additional research in this area.

Re-emergent human adenovirus genome type 7d caused an acute respiratory disease outbreak in Southern China after a twenty-one year absence.

Human adenoviruses (HAdVs) are highly contagious pathogens causing acute respiratory disease (ARD), among other illnesses. Of the ARD genotypes, HAdV-7 presents with more severe morbidity and higher mortality than the others. We report the isolation and identification of a genome type HAdV-7d (DG01_2011) from a recent outbreak in Southern China. Genome sequencing, phylogenetic analysis, and restriction endonuclease analysis (REA) comparisons with past pathogens indicate HAdV-7d has re-emerged in Southern China after an absence of twenty-one years. Recombination analysis reveals this genome differs from the 1950s-era prototype and vaccine strains by a lateral gene transfer, substituting the coding region for the L1 52/55 kDa DNA packaging protein from HAdV-16. DG01_2011 descends from both a strain circulating in Southwestern China (2010) and a strain from Shaanxi causing a fatality and outbreak (Northwestern China; 2009). Due to the higher morbidity and mortality rates associated with HAdV-7, the surveillance, identification, and characterization of these strains in population-dense China by REA and/or whole genome sequencing are strongly indicated. With these accurate identifications of specific HAdV types and an epidemiological database of regional HAdV pathogens, along with the HAdV genome stability noted across time and space, the development, availability, and deployment of appropriate vaccines are needed.

Simian adenovirus type 35 has a recombinant genome comprising human and simian adenovirus sequences, which predicts its potential emergence as a human respiratory pathogen.

Emergent human and simian adenoviruses (HAdVs) may arise from genome recombination. Computational analysis of SAdV type 35 reveals a genome comprising a chassis with elements mostly from two simian adenoviruses, SAdV-B21 and -B27, and regions of high sequence similarity shared with HAdV-B21 and HAdV-B16. Although recombination direction cannot be determined, the presence of these regions suggests prior infections of humans by an ancestor of SAdV-B35, and/or vice versa. Absence of this virus in humans may reflect non-optimal conditions for zoonosis or incomplete typing, e.g., limited epitope-based. The presence of both a critical viral replication element found in HAdV genomes and genes that are highly similar to ones in HAdVs suggest the potential to establish in a human host. This allows a prediction that this virus may be a nascent human respiratory pathogen. The recombination potential of human and simian adenovirus genomes should be considered in the use of SAdVs as vectors for gene delivery in humans.

Computational analysis of four human adenovirus type 4 genomes reveals molecular evolution through two interspecies recombination events.

Computational analysis of human adenovirus type 4 (HAdV-E4), a pathogen that is the only HAdV member of species E, provides insights into its zoonotic origin and molecular adaptation. Its genome encodes a domain of the major capsid protein, hexon, from HAdV-B16 recombined into the genome chassis of a simian adenovirus. Genomes of two recent field strains provide a clue to its adaptation to the new host: recombination of a NF-I binding site motif, which is required for efficient viral replication, from another HAdV genome. This motif is absent in the chimpanzee adenoviruses and the HAdV-E4 prototype, but is conserved amongst other HAdVs. This is the first report of an interspecies recombination event for HAdVs, and the first documentation of a lateral partial gene transfer from a chimpanzee AdV. The potential for such recombination events are important when considering chimpanzee adenoviruses as candidate gene delivery vectors for human patients.

Computational and serologic analysis of novel and known viruses in species human adenovirus D in which serology and genomics do not correlate.

In November of 2007 a human adenovirus (HAdV) was isolated from a bronchoalveolar lavage (BAL) sample recovered from a biopsy of an AIDS patient who presented with fever, cough, tachycardia, and expiratory wheezes. To better understand the isolated virus, the genome was sequenced and analyzed using bioinformatic and phylogenomic analysis. The results suggest that this novel virus, which is provisionally named HAdV-D59, may have been created from multiple recombination events. Specifically, the penton, hexon, and fiber genes have high nucleotide identity to HAdV-D19C, HAdV-D25, and HAdV-D56, respectively. Serological results demonstrated that HAdV-D59 has a neutralization profile that is similar yet not identical to that of HAdV-D25. Furthermore, we observed a two-fold difference between the ability of HAdV-D15 and HAdV-D25 to be neutralized by reciprocal antiserum indicating that the two hexon proteins may be more similar in epitopic conformation than previously assumed. In contrast, hexon loops 1 and 2 of HAdV-D15 and HAdV-D25 share 79.13 and 92.56 percent nucleotide identity, respectively. These data suggest that serology and genomics do not always correlate.

Computational analysis of adenovirus serotype 5 (HAdV-C5) from an HAdV coinfection shows genome stability after 45 years of circulation.

Adenovirus coinfections present opportunities for genome recombination. Computational analysis of an HAdV-C5 field strain genome, recovered from a patient with acute respiratory disease and coinfected with HAdV-B21, shows that there was no exchange of genomic material into HAdV-C5. Comparison of this genome to the sparsely amplified prototype demonstrates a high level of sequence conservation and stability of this genome across 45 years. Further, comparison to a version of the prototype that had been passaged in laboratory settings shows stability as well. HAdV genome stability and evolution are considerations for applications as vaccines and as vectors for gene delivery. In the annotation analysis, a single sequencing error in the HAdV-C5_ARM (Adenovirus Reference Material) genome is noted and may lead to erroneous annotation and biological interpretations.

Natural variants of human adenovirus type 3 provide evidence for relative genome stability across time and geographic space.

Human adenovirus type 3 (HAdV-B3) has an apparently stable genome yet remains a major circulating and problematic respiratory pathogen. Comparisons of the prototype genome to genomes from three current field strains, including two isolated from epidemics, and a laboratory strain, yielded small-scale nucleotide variations across 50 years of time and space (U.S. and China). This is in contrast to the recombination events that have been reported recently for HAdV genomes. Recombinant genomes have been identified in emergent HAdV pathogens and is a pathway for the molecular evolution of types. These two contrasting views of HAdV genome stability have repercussions in the development and use of vaccines for countering HAdV-B3, as well as in the continued effectiveness of vaccines developed against earlier and current circulating types of HAdV.

Applying genomic and bioinformatic resources to human adenovirus genomes for use in vaccine development and for applications in vector development for gene delivery.

Technological advances and increasingly cost-effect methodologies in DNA sequencing and computational analysis are providing genome and proteome data for human adenovirus research. Applying these tools, data and derived knowledge to the development of vaccines against these pathogens will provide effective prophylactics. The same data and approaches can be applied to vector development for gene delivery in gene therapy and vaccine delivery protocols. Examination of several field strain genomes and their analyses provide examples of data that are available using these approaches. An example of the development of HAdV-B3 both as a vaccine and also as a vector is presented.