BACKGROUND: Viral vector-based therapeutic gene therapy is a potent strategy to enhance the intrinsic reparative abilities of human orthopaedic tissues. However, clinical application of viral gene transfer remains hindered by detrimental responses in the host against such vectors (immunogenic responses, vector dissemination to nontarget locations). Combining viral gene therapy techniques with tissue engineering procedures may offer strong tools to improve the current systems for applications in vivo. METHODS: The goal of this work is to provide an overview of the most recent systems exploiting biomaterial technologies and therapeutic viral gene transfer in human orthopaedic regenerative medicine. RESULTS: Integration of tissue engineering platforms with viral gene vectors is an active area of research in orthopaedics as a means to overcome the obstacles precluding effective viral gene therapy. CONCLUSION: In light of promising preclinical data that may rapidly expand in a close future, biomaterial-guided viral gene therapy has a strong potential for translation in the field of human orthopaedic regenerative medicine.
Biocompatible Materials ; Genes, Viral ; Genetic Therapy ; Humans ; Regenerative Medicine ; Tissue Engineering

Objective: To understand the prevalence of drug resistance in treatment-naive injecting drug users (IDUs) infected with HIV-1 in Guangzhou. Methods: HIV-1 RNA were extracted from the serum specimens of the newly confirmed HIV-1 positive IDUs living in Guangzhou, being infected through injecting drug use and receiving no antiretroviral therapy at the time of confirmation during 2008-2015. Full sequence of pol protease (PR) gene and partial sequence of reverse transcriptase (RT) gene were amplified by nested reverse transcription polymerase chain reaction (nested-PCR) and sequenced. After that, data were submitted to the HIV resistance database of Stanford University for drug resistance analysis. Results: Among the 518 HIV-1 infected IDUs, HIV-1pol gene segments were successfully obtained from the serum samples of 407 HIV-1 infected IDUs (78.57%) aged 18-64 (37.44±8.14) years. Among them, males accounted for 89.68% (365/407), those of Han ethnic group accounted for 89.93% (366/407), the unmarried accounted for 55.28% (225/407), and those with education level of junior high school or below accounted for 83.78% (341/407). The distribution of subtypes was predominated by CRF07_BC (47.18%, 192/407), followed by CRF01_AE (23.83%, 97/407), CRF08_BC (22.85%, 93/407), and other subtypes (6.14%, 25/407). The overall prevalence of drug resistance was 3.44% (14/407). The prevalence of drug resistance to protease inhibitors, nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors were 1.47%(6/407), 0.25% (1/407) and 1.72% (7/407) respectively. The mutation rate was 12.29% (50/407). No major drug resistance mutation was detected in protease and nucleoside reverse transcriptase regions. Higher rate of V179E mutation in the non-nucleoside reverse transcriptase region was detected in other subtypes and subtype CRF07_BC. Mutation seemed to have occurred in all 8 cases of subtype CRF55_01B in other subtypes. The highest mutation rate of E138A was detected in subtype CRF08_BC (3.23%). Two cases were resistant to all four drugs of NNRTIs. Conclusions: The prevalence of drug resistance in treatment-naive HIV-1 positive IDUs remained at a relatively low level during 2008-2015, in Guangzhou. Most infections were sensitive to existing antiviral drugs. However, drug resistance surveillance in IDUs infected with HIV should be strengthened to prevent the prevalence of multi-drug resistance and cross drug resistance.
Adolescent ; Adult ; Child ; Drug Resistance, Viral/genetics* ; Drug Users ; Genes, pol/genetics* ; Genotype ; HIV Infections/psychology* ; HIV-1/isolation & purification* ; Humans ; Male ; Mutation ; Prevalence ; RNA, Viral/genetics* ; Young Adult

Objective: To understand the epidemiological characteristics of one large HIV molecular transmission cluster in Jiaxing city, Zhejiang province, 2017 in order to select those people under high-risk and providing basis for programs on prevention. Methods: During 2017, newly diagnosed HIV/AIDS cases in this city were recruited. Plasma samples were collected from subjects, followed by RNA extraction, RT-PCR and nest-PCR for pol gene amplification, before being sequenced and aligned. Mega 6.0 software was used to construct phylogenetic tree, and Cytoscape 3.6.0 software was used to identify HIV molecular transmission clusters. Cases within the large transmission clusters were investigated, using a field-epidemiology-questionnaire. Data related to socio-demographics and previous sexual behaviors were collected and EpiData 3.0 and SPSS 20.0 software were used. Results: In the large transmission cluster with subtype identified as CRF07_BC, in Jiaxing, 2017, 26 cases of the total 30 cases were investigated. A total of 80.8% (21/26) could be identified as newly infected within the last two years and 30.8%(8/26) could be identified as newly infected within the last one year, including 22 cases infected locally. Among several infected cases who were at age 45 years or older, they admitted that they had experienced unprotected sexual contacts in local city for long time and having had more than 10 disclosed sexual contacts within the last two years at the local venues. Conclusions: This molecular cluster had been formed and scaled up quickly in recent two years, it has played an important role in promoting and scaling up the HIV transmission. Three cases identificed as high risk played an importantrde role in scaling up this cluster.
Amplified Fragment Length Polymorphism Analysis ; China/epidemiology* ; Genes, pol ; Genotype ; HIV Infections/transmission* ; HIV-1/isolation & purification* ; Humans ; Molecular Epidemiology ; Phylogeny ; Polymerase Chain Reaction ; RNA, Viral/blood* ; Sexual Behavior ; pol Gene Products, Human Immunodeficiency Virus

Lyssaviruses, including Rabies virus, Duvenhage virus, European bat lyssavirus 1, European bat lyssavirus 2, Australian bat lyssavirus, and Irkut virus (IRKV), have caused human fatalities, but infection of IRKV in dogs has not been previously reported. In China, a dead dog that previously bit a human was determined to be infected with IRKV. Pathogenicity tests revealed that IRKVs can cause rabies-like disease in dogs and cats after laboratory infection. The close relationship between humans and pets, such as dogs and cats, may generate a new spillover-spreading route for IRKV infection. Therefore, additional attention should be paid to trans-species infection of IRKV between bats and dogs or dogs and humans through investigation of the prevalence and circulation patterns of IRKV in China.
Animals ; China ; Disease Transmission, Infectious ; Disease Vectors ; Dog Diseases ; transmission ; virology ; Dogs ; Genes, Viral ; Humans ; Lyssavirus ; genetics ; isolation & purification ; pathogenicity ; Male ; Phylogeny ; Rhabdoviridae Infections ; transmission ; veterinary ; virology

Porcine epidemic diarrhea virus (PEDV) is a highly infectious pathogen that can cause severe diseases in pigs and result in enormous economic losses in the worldwide swine industry. Previous studies revealed that PEDV exhibits an obvious capacity for modulating interferon (IFN) signaling or expression. The newly discovered type III IFN, which plays a crucial role in antiviral immunity, has strong antiviral activity against PEDV proliferation in IPEC-J2 cells. In this study, we aimed to investigate the effect of PEDV nucleocapsid (N) protein on type III IFN-λ. We found that the N proteins of ten PEDV strains isolated between 2013 and 2017 from different local farms shared high nucleotide identities, while the N protein of the CV777 vaccine strain formed a monophyletic branch in the phylogenetic tree. The N protein of the epidemic strain could antagonize type III IFN, but not type I or type II IFN expression induced by polyinosinic-polycytidylic acid (poly(I:C)) in IPEC-J2 cells. Subsequently, we demonstrated that the inhibition of poly(I:C)-induced IFN-λ3 production by PEDV N protein was dependent on the blocking of nuclear factor-κB (NF-κB) nuclear translocation. These findings might help increase understanding of the pathogenesis of PEDV and its mechanisms for evading the host immune response.
Active Transport, Cell Nucleus ; Animals ; Coronavirus Infections ; immunology ; veterinary ; virology ; Genes, Viral ; Host-Pathogen Interactions ; immunology ; Interferons ; antagonists & inhibitors ; biosynthesis ; genetics ; Interleukins ; antagonists & inhibitors ; biosynthesis ; genetics ; NF-kappa B ; metabolism ; Nucleocapsid Proteins ; genetics ; immunology ; physiology ; Porcine epidemic diarrhea virus ; genetics ; pathogenicity ; physiology ; Promoter Regions, Genetic ; Swine ; Swine Diseases ; immunology ; virology

We report the recovery of a 7068-nt viral sequence from the "viral fossils" embedded in the genome of Alhagi sparsifolia, a typical desert plant. Although the full viral genome remains to be completed, the putative genome structure, the deduced amino acids and phylogenetic analysis unambiguously demonstrate that this viral sequence represents a novel species of the genus Badnavirus. The putative virus is tentatively termed Alhagi bacilliform virus (ABV). Southern blotting and inverse polymerase chain reaction (PCR) data indicate that the ABV-related sequence is integrated into the A. sparsifolia genome, and probably does not give rise to functional episomal virus. Molecular evidence that the ABV sequence exists widely in A. sparsifolia is also presented. To our knowledge, this is the first endogenous badnavirus identified from plants in the Gobi desert, and may provide new clues on the evolution, geographical distribution as well as the host range of the badnaviruses.
Badnavirus/genetics* ; Biological Evolution ; Desert Climate ; Fabaceae/virology* ; Genes, Plant ; Genetic Variation ; Genome, Viral ; Geography ; Open Reading Frames ; Phylogeny ; Plant Diseases/virology* ; Plasmids ; Sequence Analysis, RNA

Objective: To understand the characteristics and dynamic of HIV-1 subtype distribution in men who have sex with men (MSM) in Guangzhou between 2008 and 2015. Methods: HIV-1 RNAs were extracted from serum samples of the individuals newly diagnosed with HIV-1 infection among MSM living in Guangzhou between 2008 and 2015. The pol gene segments of HIV-1 genome from these RNA samples were amplified by nested reverse transcription polymerase chain reaction (nested-PCR) and were sequenced. Subsequently, the phylogenetic tree was reconstructed using pol sequences of samples and references together and the subtype of HIV-1 was determined. The distributions of HIV-1 subtypes detected in MSM with different demographic characteristics in different years were compared. Results: A total of 2 210 pol gene segments were successfully obtained from 2 473 serum samples of the MSM. The average age of 2 210 MSM was 30.19 years with standard deviation of 8.22 years, the unmarried MSM and those in Han ethnic group accounted for 73.39% and 90.81%, respectively. The proportion of subtype CRF07_BC (38.10%) was highest, followed by CRF01_AE (34.84%), CRF55_01B (14.62%), B (6.06%), URFs (3.58%), CRF59_01B (2.17%) and other subtypes (0.63%). The annual proportions of subtype B (P=0.000, 99%CI:0.000-0.000), CRF07_BC (χ(2)=14.965, P=0.036), CRF55_01B (χ(2)=18.161, P=0.011) and URFs (P=0.001, 99% CI: 0.000-0.001) were significantly different. The proportion of subtype B showed a gradual decrease from 14.08% to 4.33% (P=0.000, 99%CI: 0.000-0.000), while the proportion of URFs rapidly increased from 0% to 6.40% (P=0.000, 99% CI: 0.000-0.000). The rate of URFs was significantly higher in farmers and migrant workers than in other groups (P=0.017, 99%CI: 0.014- 0.020) and the rate of URFs was higher in individuals who had multi sexual partners (χ(2)=5.733, P=0.017). Conclusions: CRF07_BC and CRF01_AE were the predominant HIV-1 subtypes and multiple subtypes co-circulated among MSM in Guangzhou between 2008 and 2015. The recombinations of HIV-1 continue to occur in MSM. Strengthening behavioral intervention for farmers, migrant workers and individuals who have multi sexual partners has the important epidemiological significance against the emerging and circulating of the novel recombinant virus among MSM in Guangzhou.
China/epidemiology* ; Genes, pol ; Genotype ; HIV Infections/virology* ; HIV Seropositivity/genetics* ; HIV-1/isolation & purification* ; Homosexuality, Male ; Humans ; Male ; Phylogeny ; Polymerase Chain Reaction ; RNA, Viral/blood* ; Sexual Behavior

Objective: To understand prevalence and transmission of transmitted drug resistance (TDR) among HIV infected men who have sex with men (MSM) in Tianjin from 2014 to 2017. Methods: A total of 225 blood samples were collected from HIV infected MSM in Tianjin from 2014 to 2017. Pol gene fragments were obtained by viral RNA extraction and nested PCR amplification. Phylogenetic and drug resistance analyses were conducted. Results: A total of 205 samples were successfully sequenced and analyzed. Based on pol sequences, 53.2% (109/205), 28.8% (59/205), 10.2% (21/205), 4.9% (10/205) and 2.9% (6/205) of the samples were positive for HIV subtypes CRF01_AE, CRF07_BC, B, CRF55_01B and unique recombinant forms (URFs). Twenty transmission clusters, including 75 sequences, were identified and 62.5% (10/16) of sequences with TDR were in 5 clusters. The prevalence of TDR was 7.8% between 2014 and 2017. The annual prevalence rate increased from 3.9% (2/51) in 2014, 5.7% (3/53) in 2015, 9.6% (5/52) in 2016 to 12.2%(6/49) in 2017, the difference was not significant (χ(2)=2.504, P=0.127). CRF01_AE and B strains had high TDR prevalence (3.4%, 7/205) and (2.9%, 6/205), respectively. The TDR mutation was mainly NNRTIs, the TDR prevalence was 6.3% (13/205). In contract, the TDR prevalence of NRTIs and PIs were 1.5% (3/205) and 1.0% (2/205) respectively. Conclusion: Results from this study suggested that the prevalence of HIV-1 TDR strains in MSM was serious in Tianjin. It is necessary to take effective prevention and control measures.
China ; Drug Resistance, Viral/genetics* ; Genes, pol ; Genotype ; HIV Infections/transmission* ; HIV Reverse Transcriptase/genetics* ; HIV Seropositivity/genetics* ; HIV-1/isolation & purification* ; Homosexuality, Male/statistics & numerical data* ; Humans ; Male ; Mutation ; Phylogeny ; Polymerase Chain Reaction ; Prevalence ; RNA, Viral/genetics* ; pol Gene Products, Human Immunodeficiency Virus/genetics*

Objective: To investigate the distribution patterns of mosquitoes, midges and related arboviruses in Sichuan province. Methods: Blood-sucking insects were collected from houses and pens, using the ultraviolet lights. Mosquito samples were classified according to morphologic characteristics and then stored at liquid nitrogen. All samples were incubated with BHK-21 and C6/36 cells for virus isolation and then detected for their viral genes. Sequences of the virus were identified and analyzed by molecular biological software, such as BioEdit 7.0.5.3, MEGA 6.0. Results: In total, 17 019 mosquitoes from 3 genera and 4 species and 12 700 midges were collected from the southeast regions of Sichuan province in 2016 and 2017. Among them, 79.4% (13 519/17 019) belonged to Culex tritaeniorhynchus with 11.1% (1 897/17 019) as Armigeres subalbatus, 5.5% (930/17 019) were Anopheles sinensis and 4.0% (673/17 019) were Anopheles sinensis 3 virus strains that isolated from Culex tritaeniorhynchus were identified as typeⅠ Japanese encephalitis virus. Seven pools of mosquitoes isolated from Hejiang county were identified Japanese encephalitis virus gene positive through PCR amplification. With 4 pool midges were detected positive for Akabane virus through PCR gene amplification while midges samples didn't have virus isolates. Conclusions: Culex tritaeniorhynchus appeared the predominant species in the southeast regions of Sichuan. Japanese encephalitis virus transmitted by mosquitoes and Akabane virus by midges were prevalent in southeast Sichuan province.
Animals ; Arboviruses ; Culicidae ; Encephalitis Virus, Japanese/isolation & purification* ; Encephalitis, Japanese/diagnosis* ; Genes, Viral ; Nucleic Acid Amplification Techniques ; Phylogeny ; Polymerase Chain Reaction

During the highly pathogenic avian influenza (HPAI) H5N8 virus outbreak in Korea, a dog in layer farm contaminated by H5N8 was reported seropositive for HPAI H5N8. To investigate the possibility of adaptation and transmission of HPAI H5N8 to dogs, we experimentally inoculated dogs with H5N8. Viral genes were weakly detected in nasal swabs and seroconversions in inoculated and contact dogs. Although the H5N8 virus did not induced severe clinical signs to dogs, the results suggest that surveillance of farm dogs should continue as a species in which the avian influenza virus may acquire infectivity to mammals through frequent contact with the virus.
Agriculture ; Animal Experimentation ; Animals ; Dogs* ; Genes, Viral ; Influenza in Birds* ; Korea ; Mammals ; Seroconversion ; Virulence