A novel duplication at the putative DNA polymerase alpha arrest site and a founder mutation in Chinese in the IVD gene underlie isovaleric acidaemia

Isovaleric acidaemia is a rare inherited organic acidaemia associated with a characteristic odour in affected patients. Fewer than 40 causative mutations have been reported to date. We report a case in a Hong Kong Chinese neonate who presented with respiratory distress and acute encephalopathy requiring aggressive resuscitation and treatment. Residual gross motor developmental delay was still observed at the age of 16 months. The child was subsequently found to harbour a known missense mutation (c.A1199G [p.Y371C]) and a novel 4-bp duplication (c.1148_1151dupGCTA [p.Y355X]) in the IVD gene. We suggest that the former is a founder mutation in the Chinese population and propose an explanation for the duplication event. Strategies that may achieve early diagnosis and prompt treatment include raising awareness of this condition, implementation of a tandem mass spectrometry neonatal screening programme, and local acquisition of appropriate medications for these metabolic diseases.published_or_final_versio

Studies of SARS virus vaccines

1. Intranasal vaccination using inactivated SARS coronavirus (SARS-CoV) vaccine with adjuvant can induce strong systemic (serum immunoglobulin [Ig] G) and respiratory tract local (tracheal-lung wash fluid IgA) antibody responses with neutralising activity. 2. RBD-Fc (protein-based vaccine) is able to induce effective neutralising antibodies able to provide protection from SARS-CoV infection in animal models. 3. A single dose of RBD-rAAV vaccination can induce adequate neutralising antibody against SARS-CoV infection. 4. Additional doses of vaccine increased the production of neutralising antibody 5-fold compared with a single dose. 5. RBD-rAAV vaccination provoked a prolonged antibody response with continually increasing levels of neutralising activity. 6. Intranasal vaccination with RBD-rAAV induced local IgA and systemic IgG neutralising antibodies and specific T-cell responses, able to protect against SARS-CoV infection in animal models. 7. When compared with the RBD-rAAV prime/boost vaccination, RBD-rAAV prime/RBD-peptide boost induced similar levels of Th1 and neutralising antibody responses that protected vaccinated mice from subsequent SARS-CoV challenges,but stronger Th2 and CTL responses. 8. Overall, our findings suggest that the inactivated vaccine, RBD-Fc and RBD-rAAV, can be further developed into effective and safe vaccines against SARS and that intranasal vaccination may be the preferred route of administration.published_or_final_versio

Identification of MicroRNA-like RNAs in Mycelial and yeast phases of the thermal dimorphic fungus Penicillium marneffei

published_or_final_versio

Studies of SARS virus vaccines

1. Intranasal vaccination using inactivated SARS coronavirus (SARS-CoV) vaccine with adjuvant can induce strong systemic (serum immunoglobulin [Ig] G) and respiratory tract local (tracheal-lung wash fluid IgA) antibody responses with neutralising activity. 2. RBD-Fc (protein-based vaccine) is able to induce effective neutralising antibodies able to provide protection from SARS-CoV infection in animal models. 3. A single dose of RBD-rAAV vaccination can induce adequate neutralising antibody against SARS-CoV infection. 4. Additional doses of vaccine increased the production of neutralising antibody 5-fold compared with a single dose. 5. RBD-rAAV vaccination provoked a prolonged antibody response with continually increasing levels of neutralising activity. 6. Intranasal vaccination with RBD-rAAV induced local IgA and systemic IgG neutralising antibodies and specific T-cell responses, able to protect against SARS-CoV infection in animal models. 7. When compared with the RBD-rAAV prime/boost vaccination, RBD-rAAV prime/RBD-peptide boost induced similar levels of Th1 and neutralising antibody responses that protected vaccinated mice from subsequent SARS-CoV challenges,but stronger Th2 and CTL responses. 8. Overall, our findings suggest that the inactivated vaccine, RBD-Fc and RBD-rAAV, can be further developed into effective and safe vaccines against SARS and that intranasal vaccination may be the preferred route of administration.published_or_final_versio

A novel peptide with potent and broad-spectrum antiviral activities against multiple respiratory viruses

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The Therapeutic Effect of Pamidronate on Lethal Avian Influenza A H7N9 Virus Infected Humanized Mice

A novel avian influenza virus H7N9 infection occurred among human populations since 2013. Although the lack of sustained human-to-human transmission limited the epidemics caused by H7N9, the late presentation of most patients and the emergence of neuraminidase-resistant strains made the development of novel antiviral strategy against H7N9 in urgent demands. In this study, we evaluated the potential of pamidronate, a pharmacological phosphoantigen that can specifically boost human Vδ2-T-cell, on treating H7N9 virus-infected humanized mice. Our results showed that intraperitoneal injection of pamidronate could potently decrease the morbidity and mortality of H7N9-infected mice through controlling both viral replication and inflammation in affected lungs. More importantly, pamidronate treatment starting from 3 days after infection could still significantly ameliorate the severity of diseases in infected mice and improve their survival chance, whereas orally oseltamivir treatment starting at the same time showed no therapeutic effects. As for the mechanisms underlying pamidronate-based therapy, our in vitro data demonstrated that its antiviral effects were partly mediated by IFN-γ secreted from human Vδ2-T cells. Meanwhile, human Vδ2-T cells could directly kill virus-infected host cells in a perforin-, granzyme B- and CD137-dependent manner. As pamidronate has been used for osteoporosis treatment for more than 20 years, pamidronate-based therapy represents for a safe and readily available option for clinical trials to treat H7N9 infection.published_or_final_versio

High Diversity of Genogroup I Picobirnaviruses in Mammals

published_or_final_versio

The Therapeutic Effect of Pamidronate on Lethal Avian Influenza A H7N9 Virus Infected Humanized Mice

A novel avian influenza virus H7N9 infection occurred among human populations since 2013. Although the lack of sustained human-to-human transmission limited the epidemics caused by H7N9, the late presentation of most patients and the emergence of neuraminidase-resistant strains made the development of novel antiviral strategy against H7N9 in urgent demands. In this study, we evaluated the potential of pamidronate, a pharmacological phosphoantigen that can specifically boost human Vδ2-T-cell, on treating H7N9 virus-infected humanized mice. Our results showed that intraperitoneal injection of pamidronate could potently decrease the morbidity and mortality of H7N9-infected mice through controlling both viral replication and inflammation in affected lungs. More importantly, pamidronate treatment starting from 3 days after infection could still significantly ameliorate the severity of diseases in infected mice and improve their survival chance, whereas orally oseltamivir treatment starting at the same time showed no therapeutic effects. As for the mechanisms underlying pamidronate-based therapy, our in vitro data demonstrated that its antiviral effects were partly mediated by IFN-γ secreted from human Vδ2-T cells. Meanwhile, human Vδ2-T cells could directly kill virus-infected host cells in a perforin-, granzyme B- and CD137-dependent manner. As pamidronate has been used for osteoporosis treatment for more than 20 years, pamidronate-based therapy represents for a safe and readily available option for clinical trials to treat H7N9 infection.published_or_final_versio

Prevalence and Risk Factors of Human Papillomavirus (HPV) Infection in Southern Chinese Women – A Population-Based Study

Background: Persistent high-risk type Human papillomavirus (HPV) infection is recognized as a necessary cause of cervical cancer. This study aimed to compare the HPV prevalence and risk factors between women residing in Hong Kong (HK) and Guangzhou (GZ) region of China. Methodology/Principal Findings: A total of 1,570 and 1,369 women were recruited from HK and GZ, respectively. The cytology samples were collected and tested for HPV infection. The overall and type-specific HPV prevalence and the potential risk factors for acquisition of HPV infection were studied. Women with normal cytology in the GZ cohort had significantly higher HPV prevalence (10%) than those in the HK cohort (6.2%, p<0.001). The patterns of the age-specific HPV prevalence were also different between the two cohorts. In the HK cohort, women at the age of 20-29 years old had the highest prevalence and a second peak was observed in the age of ≥60 years old. In the GZ cohort, the highest HPV prevalence was also observed in 20-29 years old but declined as the age increased and a second peak was not seen. HPV16 and HPV52 were the most common high-risk types found in the HK and GZ cohorts, respectively. Age was the most consistently observed independent risk factor for HPV infection in the HK, while the number of sexual partners had association in the GZ cohort. Conclusions/Significance: Our study provides the current status and the epidemiological characteristics of HPV prevalence in Southern Chinese women. The results strongly suggested that population education and the effective cervical cancer screening would be vital in the prevention of cervical cancer. © 2011 Liu et al.published_or_final_versio