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Molecular characterization of human coronaviruses and their circulation dynamics in Kenya, 2009–2012

Molecular characterization of human coronaviruses and their circulation dynamics in Kenya, 2009–2012

Coronaviruses cause various diseases in different hosts, such as respiratory tract infections, gastroenteritis, hepa- titis, and encephalomyelitis in birds and mammals [5]. Coronaviruses are classified into four distinct phylogenetic groups. Whereas alphacoronaviruses, betacoronaviruses and gammacoronaviruses infect mammals, deltacorona- viruses infect avian species [6]. All known human corona- viruses (HCoV) belong to the alphacoronavirus and betacoronaviruses. HCoV cause 30 % of common colds as well as severe infections in infants, children, and immuno- compromised persons and the elderly [7]. HCoVs have a worldwide circulation, with reports published in popula- tions of different countries such as Saudi Arabia [8], France [9], Kenya [10] and China [11] among others. However in 2012, a novel betacoronavirus Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was iso- lated in Jeddah from a patient who was suffering from pneumonia and later died [8]. This MERS-CoV continues to cause fatal severe lower respiratory tract illnesses in various parts of the world, especially in the Middle East. As of February 2015, the World Health Organization had reported 971 laboratory confirmed cases with 356 deaths [12]. In light of the finding of this previously unknown coronavirus, it is probable that coronaviruses, other than those recognized to date, may be circulating in human populations in Kenya. As human coronaviruses are not routinely analyzed in Kenya, this study sought to identify and characterize HCoV strains circulating in different parts of Kenya and thus provide a knowledge base for epi- demiological importance of human coronaviruses.
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Prevalence of Antibodies to Four Human Coronaviruses Is Lower in Nasal Secretions than in Serum

Prevalence of Antibodies to Four Human Coronaviruses Is Lower in Nasal Secretions than in Serum

Little is known about the prevalence of mucosal antibodies induced by infection with human coronaviruses (HCoV), including HCoV-229E and -OC43 and recently described strains (HCoV-NL63 and -HKU1). By enzyme-linked immunosorbent assay, we measured anti-HCoV IgG antibodies in serum and IgA antibodies in nasal wash specimens collected at seven U.S. sites from 105 adults aged 50 years and older (mean age, 67 ⴞ 9 years) with chronic obstructive pulmonary disease. Most patients (95 [90%]) had at least one more chronic disease. More patients had serum antibody to each HCoV strain (104 [99%] had antibody to HCoV-229E, 105 [100%] had antibody to HCoV-OC43, 103 [98%] had antibody to HCoV-NL63, and 96 [91%] had antibody to HCoV-HKU1) than had antibody to each HCoV strain in nasal wash specimens (12 [11%] had antibody to HCoV-229E, 22 [22%] had antibody to HCoV-OC43, 8 [8%] had antibody to HCoV-NL63, and 31 [31%] had antibody to HCoV-HKU1), respectively (P < 0.0001). The proportions of subjects with IgA antibodies in nasal wash specimens and the geometric mean IgA antibody titers were statistically higher for HCoV-OC43 and -HKU1 than for HCoV-229E and -NL63. A higher proportion of patients with heart disease than not had IgA antibodies to HCoV-NL63 (6 [16%] versus 2 [3%]; P ⴝ 0.014). Correlations were highest for serum antibody titers between group I strains (HCoV-229E and -NL63 [r ⴝ 0.443; P < 0.0001]) and between group II strains (HCoV-OC43 and -HKU1 [r ⴝ 0.603; P < 0.0001]) and not statistically significant between HCoV-NL63 and -OC43 and between HCoV-NL63 and -HKU1. Patients likely had experienced infections with more than one HCoV strain, and IgG antibodies to these HCoV strains in serum were more likely to be detected than IgA antibodies to these HCoV strains in nasal wash specimens.
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The Novel Human Coronaviruses NL63 and HKU1

The Novel Human Coronaviruses NL63 and HKU1

By infecting healthy volunteers, researchers learned that in- fection with HCoV-229E or HCoV-OC43 results in a common cold (7, 8, 29), and since then, HCoVs have been considered to be relatively harmless respiratory pathogens. This image was roughly disturbed when severe acute respiratory syndrome (SARS)-CoV was introduced into the human population in the winter of 2002 to 2003 in China. SARS-CoV causes a severe respiratory illness with high morbidity and mortality (16, 40). The virus originated from a wild-animal reservoir, most likely bats (43, 46), and was transmitted to humans via infected civet cats. The epidemic was halted in 2003 by a highly effective global public health response, and SARS-CoV is not currently circulating in humans. However, the SARS outbreak brought coronaviruses back into the limelight, and a renewed interest in this virus family resulted in the identification of two more human coronaviruses. We discovered HCoV-NL63, a novel member of group I, in a child with bronchiolitis in The Neth- erlands (74). HCoV-HKU1, a novel group II virus from an adult with chronic pulmonary disease in Hong Kong, was de- scribed in 2005 (81). An animal model is currently lacking for these previously unknown viruses. Nevertheless, since the dis- covery of HCoV-NL63 and HCoV-HKU1, much knowledge about these viruses has been gained. Several groups have stud- ied their worldwide spread, association with human disease, replication characteristics, genome organization, and genetic diversity.
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Prevalence and genetic diversity analysis of human coronaviruses among cross border children

Prevalence and genetic diversity analysis of human coronaviruses among cross border children

Human coronaviruses (HCoVs) have been causing world- wide outbreak with cases of hospitalization [1]. Six types of coronaviruses (CoVs) are known to infect human: two α -CoVs, i.e. 229E and NL63, two β -CoVs group A, i.e. HKU1 and OC43, β -CoVs group B, i.e. Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and β -CoVs group C, i.e. Middle East Respiratory Syndrome Coronavirus (MERS-CoV). SARS-CoV and MERS-CoV, which are highly pathogenic to human lives and have caused serious diseases or death, causes about 10 and 36% mortality respectively. OC43, HKU1, NL63 and 229E are the most common four HCoVs in most regions, circulating worldwide with a detection rate ranging from 1.1 - 8.5% and with variations in their predominantly circulating seasons and strains [2 – 5]. HCoVs ranks the third in the detection rate of all 17 respiratory viruses in south of China (Guangzhou) and poses a heavy burden to the health care of children as it is associated with acute upper or lower respiratory tract infections, and cases of death have been reported [6]. Moreover, high mutation rates caused by the low fidelity of RNA-dependent RNA polymerase (RdRp) led to high diversity of HCoVs [7]. Several studies about the genetic diversity of human coro- naviruses on hospitalized patients had been carried out previously. The new OC43 genotype D based on the recombination of B and C was discovered in 2005 [8]. Two additional recombinants: E (CH) and E (FR) were reported as homologous genome recombination in 2015 [9, 10]. The genetic features of NL63 were reported at least three distinct circulating genotypes (A, B and C) and one recombinant (cluster R) in the United States in 2011 [11]. Meanwhile, HKU1 strains were grouped into three clusters (A, B and C) due to natural recombination [12]. These previous reports focused on hospitalized patients, who have low mobility and seldom cross the border, while this study hereby firstly reports the analysis on cross- border children, mainly including “ cross-boundary students ” , who are born and attend school in Hong Kong but reside in Mainland China [13, 14]. A border still exists between Shenzhen in Mainland China and Hong Kong (SZ-HK port) due to the colonial history, resulting in different health care and education sys- tems [13]. Children had a high incidence of coronaviruses
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Infection of primary cultures of human neural cells by human coronaviruses 229E and OC43.

Infection of primary cultures of human neural cells by human coronaviruses 229E and OC43.

Human coronaviruses (HCVs) cause up to one-third of com- mon colds (14) and have been occasionally associated with multiple sclerosis (MS), an inflammatory demyelinating dis- ease of the central nervous system (CNS), together with sev- eral other viruses (21). For example, coronaviruses SD and SK were isolated from brain samples of MS patients (1). Even though these isolates are likely murine contaminants (25), in vivo experiments in nonhuman primates have shown that the SD isolate can, after intracerebral inoculation, cause a sub- acute panencephalitis and that demyelination can be observed in brain sections from autopsy samples (13). Moreover, a neu- rotropic murine coronavirus was shown to enter the CNS of primates after peripheral inoculation (3). Other studies have reported the detection of HCV RNA in the CNS of MS pa- tients (12, 20) and of coronavirus-myelin cross-reactive T cells in MS patients but not control subjects (24). Serological data showed a significant difference between MS patients and con- trol subjects in titers of anticoronavirus antibodies in the ce- rebrospinal fluid (18). Although the neurotropism of corona- viruses in humans has not yet been proven (23), various continuous human neural cell lines have been shown to be susceptible to HCV infection (4, 22), and a preliminary study with HCV OC43 in mixed primary neural cultures suggested that human fetal astrocytes were possibly susceptible to infec- tion (17).
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From SARS and MERS to COVID-19: a brief summary and comparison of severe acute respiratory infections caused by three highly pathogenic human coronaviruses

From SARS and MERS to COVID-19: a brief summary and comparison of severe acute respiratory infections caused by three highly pathogenic human coronaviruses

Within two decades, there have emerged three highly pathogenic and deadly human coronaviruses, namely SARS- CoV, MERS-CoV and SARS-CoV-2. The economic burden and health threats caused by these coronaviruses are extremely dreadful and getting more serious as the increasing number of global infections and attributed deaths of SARS-CoV-2 and MERS-CoV. Unfortunately, specific medical countermeasures for these hCoVs remain absent. Moreover, the fast spread of misinformation about the ongoing SARS-CoV-2 pandemic uniquely places the virus alongside an annoying infodemic and causes unnecessary worldwide panic. SARS-CoV-2 shares many similarities with SARS-CoV and MERS-CoV, certainly, obvious differences exist as well. Lessons learnt from SARS-CoV and MERS- CoV, timely updated information of SARS-CoV-2 and MERS-CoV, and summarized specific knowledge of these hCoVs are extremely invaluable for effectively and efficiently contain the outbreak of SARS-CoV-2 and MERS-CoV. By gaining a deeper understanding of hCoVs and the illnesses caused by them, we can bridge knowledge gaps, provide cultural weapons for fighting and controling the spread of MERS-CoV and SARS-CoV-2, and prepare effective and robust defense lines against hCoVs that may emerge or reemerge in the future. To this end, the state- of-the-art knowledge and comparing the biological features of these lethal hCoVs and the clinical characteristics of illnesses caused by them are systematically summarized in the review.
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<p>Molecular Basis for Pathogenicity of Human Coronaviruses</p>

<p>Molecular Basis for Pathogenicity of Human Coronaviruses</p>

Although by molecular analysis, SARS-CoV-2 and SARS-CoV were put in different groups, they still pos- sessed around 50 conserved amino acids in the S1 subunit, whereas most of the bat-derived viruses displayed muta- tional differences in this position interacting with ACE2. Most of the mutational differences between SARS-CoV-2 and bat-SL-CoVs were positioned in the S1-CTD, where the RBD of ß-CoVs is located and directly engages the protein receptor as in SARS-CoV from lineage B and MERS-CoV from lineage C (Figure 2). In comparison to SARS-CoV-2, several deletions, including positions 455 – 457, 463 – 464, and 485 – 497, existed in the RBD of S protein obtained from bat-derived strains. 1,3,10,23 Despite the high homology in spike sequence, there were differ- ences in the fi ve most important amino acids (L465, L495, Y502, D510, and H514) in bat-SL-CoV RBD from SARS- CoV-2 and SARS-CoV RBD, exhibited natural selections in SARS-CoV and SARS-CoV-2 which played critical roles in the cross-species transmission of SARS-CoV-2 and SARS-CoV to humans. 23,30 Several key residues responsible for the binding of the SARS-CoV RBM to the ACE2 receptor were variable in the SARS-CoV-2 RBM (including Ala426/Asn439, Thr487/Asn501, Asp479/Gln493, Gly485, and Leu472/Phe486; SARS- CoV/SARS-CoV-2 numbering). 1,23 Critical residues in SARS-CoV-2 RBM (particularly Gln493) provide favor- able interactions with human ACE2, consistent with SARS-CoV-2 ’ s capacity for human cell infection. Other variable residues in SARS-CoV-2 RBM Asn501 is compa- tible with, but not ideal for, binding human ACE2, sug- gesting that SARS-CoV-2 has mutated and acquired some capacity for human-to-human transmission. Potentially recognizing ACE2 from a diversity of animal species
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Surveillance of Bat Coronaviruses in Kenya Identifies Relatives of Human Coronaviruses NL63 and 229E and Their Recombination History

Surveillance of Bat Coronaviruses in Kenya Identifies Relatives of Human Coronaviruses NL63 and 229E and Their Recombination History

The phylogeny suggests both ancient virus-host codivergence and recent cross- species transmission of CoVs between bats and other mammalian hosts. The phylogeny clearly demonstrates that CoVs from two host groups, one dominated by bats and the other exclusively by nonchiropteran mammals, formed sister clades for both alpha- and beta-CoVs (Fig. 3), suggestive of an ancient divergence between them. Conversely, several nonchiropteran CoVs are nested within the diversity of bat CoVs, suggesting that these viruses are relatively recent introductions from bats. These cross-species transmission events resulted in the emergence of severe (SARS-CoV and MERS-CoV) and mild (HCoV-NL63 and HCoV-229E) human pathogens, as well as animal pathogens (porcine epidemic diarrhea virus [PEDV] and alpaca respiratory CoV). Interestingly, HCoV-NL63, previously thought to be related to the North American tricolored bat (P. subflavus) (19), in our phylogeny is deeply nested within the newly identified CoVs from African Triaenops afer bats (Fig. 3), while the P. subflavus virus (labeled green in Fig. 3) grouped with a North American CoV sampled from a Myotis volans bat (Fig. 3). Therefore, Triaenops afer bats likely represent the most recent chiropteran reservoir host of viruses ancestral to HCoV-NL63. In addition, our results identified 16 additional 229E-like viruses (Fig. 2, L14), providing further evidence that Hipposideros bats in Africa harbor viruses that are ancestral to HCoV-229E (5, 6).
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Plaque assay and improved yield of human coronaviruses in a human rhabdomyosarcoma cell line

Plaque assay and improved yield of human coronaviruses in a human rhabdomyosarcoma cell line

Propagation and plaque assay of human coronavirus prototypes were studied in two human cell lines: a diploid fetal tonsil FT and a heteroploid rhabdomyosarcoma RD cell line.. Plaques, ob[r]

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Quantitation of Antibody to Non Hemagglutinating Viruses by Single Radial Hemolysis: Serological Test for Human Coronaviruses

Quantitation of Antibody to Non Hemagglutinating Viruses by Single Radial Hemolysis: Serological Test for Human Coronaviruses

To show the general application of the SRH test for antibodies to non-hemagglutinating viruses, it was applied to human coronavirus 229E, the mouse hepatitis virus coronaviruses, coxsack[r]

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Antigenic characterization of human coronaviruses 229E and OC43 by enzyme linked immunosorbent assay

Antigenic characterization of human coronaviruses 229E and OC43 by enzyme linked immunosorbent assay

The relative sensitivity of ELISA when compared with other tests used for measurement of antibody titers to specific coronavirus antigens in both hyperimmune rabbit and human convalescen[r]

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Bat origin of human coronaviruses

Bat origin of human coronaviruses

During our longitudinal surveillance at a Rhinolophus sinicus colony in Yunnan Province over the years, a major breakthrough came in 2013 when diverse SL- CoVs were discovered in the single colony [53]. In this colony, there were at least 7 different strains related to SARS-CoV, HKU3, Rs672 or Rf1, based on analysis of the region corresponding to SARS-CoV RBD. Intri- guingly, unlike all previously described SL-CoVs, two strains, designated Rs3367 and RsSHC014, did not con- tain the deletions in this region. Rs3367 showed a par- ticularly high sequence identity to SARS-CoV in RBD and was identical to SARS-CoV in several key amino acid residues known to be important for receptor bind- ing [53]. Whole genome sequencing revealed that Rs3367 and RsSHC014 shared more than 95 % genome sequence identity with human and civet SARS-CoV, which was remarkably higher than that of any other bat SL-CoV (76 to 92 %). Regarding individual genes, the amino acid sequence identity between Rs3367 or RsSHC014 and SARS-CoV was higher than 96 % in ORF1a, 1b, 3a, 3b, E, M and N genes [53]. Most import- antly, a live SL-CoV was isolated for the first time from bat fecal samples [53]. This virus, termed WIV1, had al- most identical sequence (99.9 %) to Rs3367 and was demonstrated to use ACE2 molecules from humans, civets and Chinese horseshoe bats for cell entry. It also displayed infectivity in cell lines from a broad range of species including human, pig, and bat. Furthermore, the close relatedness between WIV1 and SARS-CoV was confirmed by neutralization effect of convalescent SARS patient sera on WIV1 [53]. The isolation of a bat SL- CoV genetically closely resembling SARS-CoV and having a functional S protein capable of using the same ACE2 receptor as SARS-CoV provided robust and con- clusive evidence for the bat origin of SARS-CoV.
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Severe Acute Respiratory Syndrome Coronavirus Group-Specific Open Reading Frames Encode Nonessential Functions for Replication in Cell Cultures and Mice

Severe Acute Respiratory Syndrome Coronavirus Group-Specific Open Reading Frames Encode Nonessential Functions for Replication in Cell Cultures and Mice

Human coronaviruses, members of the Nidovirus order, have been divided into several genogroups (7). The group I coro- naviruses include human coronavirus 229E (HCV-229E), which is typically associated with the common cold. A second group I coronavirus, HCV-NL63, causes more severe lower respiratory tract disease in infants, children, and adults, world- wide (18, 64), and may also be associated with Kawasaki dis- ease (16). The group II human coronaviruses include HCV- OC43, which has typically been associated with common colds in winter and occasional lower respiratory tract infections in children and adults, and the recently described HKU1, which was identified in two adults with pneumonia (68). However, the overall epidemiology and severity of HKU1 infection in hu- mans remains undefined. Phylogenetic analyses have suggested that SARS-CoV either represents the prototype group IV coronavirus or can be classified as an early split-off of group II (36, 48, 54). SARS-CoV-like viruses have been isolated from civet cats, raccoon dogs, and pigs, but the civet cat is a likely reservoir (22). Molecular evolutionary studies on isolates ob- tained from different stages in the outbreak have implicated * Corresponding author. Mailing address: Department of Epidemi-
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1430-05.pdf

1430-05.pdf

Human coronaviruses, members of the Nidovirus order, have been divided into several genogroups (7). The group I coro- naviruses include human coronavirus 229E (HCV-229E), which is typically associated with the common cold. A second group I coronavirus, HCV-NL63, causes more severe lower respiratory tract disease in infants, children, and adults, world- wide (18, 64), and may also be associated with Kawasaki dis- ease (16). The group II human coronaviruses include HCV- OC43, which has typically been associated with common colds in winter and occasional lower respiratory tract infections in children and adults, and the recently described HKU1, which was identified in two adults with pneumonia (68). However, the overall epidemiology and severity of HKU1 infection in hu- mans remains undefined. Phylogenetic analyses have suggested that SARS-CoV either represents the prototype group IV coronavirus or can be classified as an early split-off of group II (36, 48, 54). SARS-CoV-like viruses have been isolated from civet cats, raccoon dogs, and pigs, but the civet cat is a likely reservoir (22). Molecular evolutionary studies on isolates ob- tained from different stages in the outbreak have implicated * Corresponding author. Mailing address: Department of Epidemi-
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Coronaviruses and the human airway: a universal system for virus host interaction studies

Coronaviruses and the human airway: a universal system for virus host interaction studies

Human coronaviruses (HCoVs) are large RNA viruses that infect the human respiratory tract. The emergence of both Severe Acute Respiratory Syndrome and Middle East Respiratory syndrome CoVs as well as the yearly circulation of four common CoVs highlights the importance of elucidating the different mechanisms employed by these viruses to evade the host immune response, determine their tropism and identify antiviral compounds. Various animal models have been established to investigate HCoV infection, including mice and non-human primates. To establish a link between the research conducted in animal models and humans, an organotypic human airway culture system, that recapitulates the human airway epithelium, has been developed. Currently, different cell culture systems are available to recapitulate the human airways, including the Air-Liquid Interface (ALI) human airway epithelium (HAE) model. Tracheobronchial HAE cultures recapitulate the primary entry point of human respiratory viruses while the alveolar model allows for elucidation of mechanisms involved in viral infection and pathogenesis in the alveoli. These organotypic human airway cultures represent a universal platform to study respiratory virus-host interaction by offering more detailed insights compared to cell lines. Additionally, the epidemic potential of this virus family highlights the need for both vaccines and antivirals. No commercial vaccine is available but various effective antivirals have been identified, some with potential for human treatment. These morphological airway cultures are also well suited for the identification of antivirals, evaluation of compound toxicity and viral inhibition.
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main__2_.pdf

main__2_.pdf

Following its emergence in 2003, SARS was quickly identified as a zoonotic virus, and the identification of the wet markets as a potential source may have assisted epidemiological control of the disease [24]. While palm civets, raccoon dogs, and horseshoe bats (Rhinolophus genus) have all been identified as hosts of SARS-like CoVs, it is suggested that only the horseshoe bats are likely reservoir hosts. Bats are widely distributed, highly diverse, and extremely mobile mammals with an estab- lished role as hosts of emergent RNA viruses. Corona- viruses occupy an exceptionally wide distribution in bats; recent surveillance studies have extended our recognition of this range to Africa, Europe, South America, and North America [4,9,25–27]. The genetic variation encoded within many recently discovered coronaviruses hosted by bats is far greater than the diversity noted between many human coronaviruses, despite a proportionally small sampling of the 1200 bat species, leading some researchers to speculate that all mammalian coronaviruses are derived from bat reservoir strains [4,28]. The exten- sive sequence diversity provides considerable opportu- nity for the emergence of new animal and human coronaviruses, which would be sufficiently antigenically distinct as to not be influenced by preexisting exposure and memory immune responses to established human CoVs. For example, little antigenic cross reactivity exists between the S glycoproteins of more distantly related group 2b bat coronaviruses and the SARS-CoV [29]. From a historic context, the next emergent event is likely dependent only on ecological and epidemiological situ- ations and time, as the viral potential is well established [30,31].
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Detection of rodent coronaviruses in tissues and cell cultures by using polymerase chain reaction

Detection of rodent coronaviruses in tissues and cell cultures by using polymerase chain reaction

Human coronaviruses HCV OC43 and 229E were obtained from the American Type Culture Collection in the form of 20% infant mouse brain homogenate and W138 cell lysate, respectively, and wer[r]

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Comparison of viral and epidemiological profiles of hospitalized children with severe acute respiratory infection in Beijing and Shanghai, China

Comparison of viral and epidemiological profiles of hospitalized children with severe acute respiratory infection in Beijing and Shanghai, China

Results: Of 700 samples, 547 (78.1%) tested positive for viral infections. The picornaviruses (PIC), which included rhinovirus (RV) and enterovirus (EV), were the most common (34.0%), followed by respiratory syncytial virus (RSV) (28.3%), human bocavirus (HBoV) (19.1%), adenovirus (ADV) (13.7%), human coronaviruses (HCoV) (10.7%), influenza A and B (8.9%), parainfluenza virus (PIV 1 – 3) (7.9%), and human metapneumovirus (HMPV) (5.0%). PIC (RV/EV) and RSV were the most prevalent etiological agents of SARI in both cities. The total and age-matched prevalence of RSV, HCoV, and hMPV among SARI children under 5 years old were significantly higher in Beijing than in Shanghai. Different age and seasonal distribution patterns of the viral infections were found between Beijing and Shanghai. Conclusions: Viral infection was tested and shown to be the most prevalent etiological agent among children with SARI in either the Beijing or the Shanghai area, while showing different patterns of viral and epidemiological profiles. Our findings provide a better understanding of the roles of geographic location and climate in respiratory viral infections in hospitalized children with SARI.
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Neuroinvasion by Human Respiratory Coronaviruses

Neuroinvasion by Human Respiratory Coronaviruses

one or both HCoV (48% of all) was relatively large. Statistical analysis of our results showed that the 229E strain was present in all groups and did not show a preferential association for women versus men or for patients with MS versus those with OND or normal controls. However, the OC43 strain was pref- erentially present in MS patients compared to those with OND (P ⫽ 0.0169) or compared to all controls (P ⫽ 0.0137) as calculated by chi-square and Fisher’s exact tests, respectively. Normal controls did not show a statistically different propor- tion of HCoV-OC43-positive brains compared to MS patients. Molecular adaptation of viral strains in human brains. To ascertain the coronaviral origin and also to verify the possible molecular adaptation of these viruses in human brain samples compared to laboratory viruses, we sequenced HCoV ampli- cons from human brains. It has been shown for the murine counterpart of HCoV, MHV, that point mutations and dele- tions arise during a persistent in vivo infection of the murine CNS (1, 44). Moreover, certain point mutations were mainly observed in animals experiencing chronic demyelinating dis- ease and rarely in asymptomatic animals (42). The viral protein N was previously shown to have mutated in the CNS of the viral host (1). We compared sequences obtained to already- published sequences for each viral strain. We did not observe point mutations or deletions among the human brain ampli- cons for the 229E strain compared to viral amplicons obtained from our positive control (RNA from infected cells). Two point mutations for the OC43 strain, one leading to an amino acid change (position 398; AGA3GGA; R3G) and the other silent (position 442; CTG3CTA) were observed in four dif- ferent brains: one normal control and three brains of MS patients. Moreover, an additional point mutation (position 261; GTA3GCA; V3A) was observed in one of the MS patient brains. These mutations were never observed in any positive controls (viral RNA from acutely infected patient cell lines). We conclude that these point mutations were probably representative of those in viral RNA present in human brains. Indeed, these changes suggest that HCoV could have adapted to the CNS, unlike the laboratory viruses, which we obtained from the American Type Culture Collection and which were initially isolated from the upper respiratory tract. Moreover,
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Human rhinovirus infection in young African children with acute wheezing

Human rhinovirus infection in young African children with acute wheezing

A general shell vial culture using a pool of monoclonal antibodies detecting respiratory syncytial virus (RSV), influenza A and B viruses, adenovirus and parainfluenza viruses 1, 2 and 3 was performed on every 4 th sample (n = 58) by an indirect immunofluorescence assay (Light Diag- nostics, Chemicon International, CA, USA). Further speci- fic virus identification on pool-positive samples was not undertaken. All samples were screened for human metap- neumovirus (hMPV), human coronavirus-NL63 (HCoV- NL63) and human bocavirus (HBoV) by RT-PCR and PCR as previously described [26].
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