Double viral vector intersectional approaches for pathway-selective manipulation of motor functions and compensatory mechanisms.

Selective manipulation of particular subcomponent of neural circuits is crucial for understanding the functional architecture of neural systems and for development of the future therapeutic strategies against neurological disorders. In this article, I review how the intersectional approaches with double viral vector technique was introduced for the pathway-selective manipulation of spinal circuits. In this technique, a retrograde gene transfer vector is injected into the terminal area of the targeted neurons and an anterograde vector is injected at the location of their somata. Either by using the Tet-transactivator or Cre-loxP system, the experimenter can chemogenetically or optogenetically manipulate the transmission of the target pathway originated from the double-infected neurons. This technique was first developed for manipulation of spinal cord interneurons in the macaque monkeys by selective expression of tetanus neurotoxin and successfully affected the dexterous hand movements. Currently, this technique is widely used on a variety of neural pathways both in rodents and primates in combination with a variety of retrograde vectors and a variety of optogenetic and chemogenetic tools. The advantage of this technique is that it is not necessary to generate transgenic animals. Knowledge of the cell-type specific promotors is not needed. Manipulation is achieved primarily by injection of two viral vectors based on the anatomical knowledge and it is applicable in a variety of animal species including primates. The pros, cons and future direction of this technique are discussed.

Epidemiological study of positive children with respiratory syncytial virus in Jiangsu / 公共卫生与预防医学

Objective To investigate the epidemiological characteristics of respiratory syncytial virus (RSV) positive children in Jiangsu, and to provide reference for the prevention and treatment of RSV infection. Methods A total of 11 574 children with respiratory tract infection from June 2018 to June 2020 were selected. RSV antigen was detected by direct immunofluorescence assay in all children. Other 6 kinds of respiratory viruses were detected in RSV positive specimens to understand the mixed infection. Results The positive rate of RSV in 11 574 samples was 12.34%(1 428/11 574), and the male to female ratio of RSV positive children was 1.92:1 (915/476). The detection rate of male children (12.79%) was significantly higher than that of female children (10.77%)(χ2=10.951, P2=27.48, P0.05). The positive rate of RSV from November to March was significantly higher than that from other months (χ2=9.451, P<0.05). The highest positive rate was 2 months (16.99%). Of the 1428 RSV-positive cases, 148 were co-infected with at least one other respiratory virus, accounting for 10.36%(148/1 428) of the RSV-positive cases. Among them, 117 cases were double infection and 31 cases were triple infection. RSV combined with PIV3 infection was the most common in 39 cases (26.35%). Conclusion RSV positive children are mainly concentrated in infants under 12 months of age in Jiangsu province, and the incidence is high from November to March. The protection of infants under 12 months of age should be strengthened, especially in hospitalized cases and male cases, which are often mixed with infection..

Influenza A Virus Inhibits RSV Infection via a Two-Wave Expression of IFIT Proteins.

Influenza viruses and respiratory syncytial virus (RSV) are respiratory viruses that primarily circulate worldwide during the autumn and winter seasons. Seasonal surveillance has shown that RSV infection generally precedes influenza. However, in the last four winter seasons (2016-2020) an overlap of the morbidity peaks of both viruses was observed in Israel, and was paralleled by significantly lower RSV infection rates. To investigate whether the influenza A virus inhibits RSV, human cervical carcinoma (HEp2) cells or mice were co-infected with influenza A and RSV. Influenza A inhibited RSV growth, both in vitro and in vivo. Mass spectrometry analysis of mouse lungs infected with influenza A identified a two-wave pattern of protein expression upregulation, which included members of the interferon-induced protein with the tetratricopeptide (IFITs) family. Interestingly, in the second wave, influenza A viruses were no longer detectable in mouse lungs. In addition, knockdown and overexpression of IFITs in HEp2 cells affected RSV multiplicity. In conclusion, influenza A infection inhibits RSV infectivity via upregulation of IFIT proteins in a two-wave modality. Understanding the immune system involvement in the interaction between influenza A and RSV viruses will contribute to the development of future treatment strategies against these viruses.

High-Risk Sexual Practices Contribute to HIV-1 Double Infection Among Men Who Have Sex with Men in Madrid.

Data on the prevalence of double infection (DI) in HIV individuals are lacking in Spain. To fill this gap, we analyzed the prevalence of DI in a cohort of men who have sex with men (MSM) and examined factors contributing to DI. We selected 81 MSM attending Centro Sanitario Sandoval, a sexually transmitted diseases clinic in Madrid. We obtained by ultra-deep sequencing the proviral sequences in gag and env genes and performed a phylogenetic analysis for the identification of DI. Clinical, behavioral, host, and viral factors were studied for its association with DI. We detected six individuals with DI and one case of superinfection with a global prevalence of 8.6%. The genetic distance among the subtype B viruses in monoinfected individuals (24.4%) was lower than the distance between the two viruses in subtype B DI individuals (29.5%). Individuals with a high number of sexual contacts (>25 partners/year) had an 8.66 times higher risk of DI (p = .017). In this MSM cohort the prevalence of HIV DI was estimated at 8.6%. DI was strongly associated with the number of sexual partners. Because of the pathogenic consequences of HIV DI, this high prevalence should promote public health programs targeted at high-risk population such as MSM for the control of HIV infection and DI. HIV DI should be considered for a better clinical management of these individuals.

Candida albicans and Staphylococcus lugdunensis superinfection of liver cysts in a patient with autosomal dominant polycystic kidney disease under prednisolone treatment.

We report a case of superinfection of liver cysts caused by Candida albicans and Staphylococcus lugdunensis in a patient with autosomal dominant polycystic kidney disease. A 69-year-old man with chief complaints of headache and blurred vision was admitted to the former institution for the evaluation of suspected temporal arteritis. He was prescribed oral prednisolone (55 mg/day) as a preemptive treatment; however, he became febrile and presented with bilateral flank pain during prednisolone tapering. Blood culture revealed fungemia as a result of Candida famata infection; thus, micafungin treatment was started. Thereafter, recrudescence of the C-reactive protein level ensued. Then a cyst infection as visualized on magnetic resonance imaging led to cyst aspiration sclerotherapy. Cyst aspirate culture revealed the presence of C. albicans in one of the cysts and S. lugdunensis in two of the cysts. The patient was clinically stabilized with an additional 3 weeks of antibiotic and antifungal drug administration.

Rotavirus Double Infection Model to Study Preventive Dietary Interventions.

Rotaviruses are the main cause of acute diarrhea among young children worldwide with an increased frequency of reinfection. Several life style factors, such as dietary components, may influence such processes by affecting the outcome of the first rotavirus infection and therefore having a beneficial impact on the anti-rotavirus immune responses during any subsequent reinfections. The aim of this research was to develop a double-infection model in rat that mimics real-life clinical scenarios and would be useful in testing whether nutritional compounds can modulate the rotavirus-associated disease and immune response. Three experimental designs and a preventive dietary-like intervention were conducted in order to achieve a differential response in the double-infected animals compared to the single-infected ones and to study the potential action of a modulatory agent in early life. Diarrhea was only observed after the first infection, with a reduction of fecal pH and fever. After the second infection an increase in body temperature was also found. The immune response against the second infection was regulated by the preventive effect of the dietary-like intervention during the first infection in terms of specific antibodies and DTH. A rotavirus-double-infection rat model has been developed and is suitable for use in future preventive dietary intervention studies.

Symbiont-conferred reproduction and fitness benefits can favour their host occurrence.

Double infections of Wolbachia and Spiroplasma are frequent in natural populations of Tetranychus truncatus, a polyphagous mite species that has been a dominant species in China since 2009. However, little is known about the causes and ecological importance of such coexistences. In this study, we established T. truncatus strains with different infection types and then inferred the impact of the two endosymbionts on host reproduction and fitness. Double infection induced cytoplasmic incompatibility, which was demonstrated by reduction in egg hatchability of incompatible crosses. However, doubly infected females produced more eggs relative to other strains. Wolbachia and Spiroplasma did not affect host survival, whereas doubly infected females and males developed faster than other strains. Such reproduction and fitness benefits provided by double infections may be associated with the lower densities of each symbiont, and the quantitative results also confirmed competition between Wolbachia and Spiroplasma in doubly infected females. These symbiont-conferred beneficial effects maintain stable prevalence of the symbionts and also help drive T. truncatus outbreaks in combination with other environmental factors.

Study on antimicrobial resistance of anti-tuberculosis drugs in patients with double infection of HIV/TB using phage bio-amplification method / 重庆医学

Objective To analyze the drug resistance status of mycobacterium tuberculosis in patients with double immunization of human immunodeficiency virus (HIV) and tuberculosis (TB) by phage bioassay (PhaB),and to optimize the control strategy.Methods One hundred and twelve cases of HIV/TB infected patients.in Chongqing Ninth People's Hospital were treated with PhaB method,and the drug susceptibility testing results were compared with 208 cases of simple pulmonary tuberculosis patients.Results The anti-tuberculosis drug resistance rate of HIV/TB patients was lower than that of simple pulmonary tuberculosis patients.The resistance rates of 5 common anti-tuberculosis drugs in HIV/TB patients were 7.14％ of isoniazid (INH),7.14％ of pyrazinamide (PZA),5.36 ％ of rifampicin(RFP) streptomycin(SM),and 4.46 ％ of ethambutol (EMB),compared with simple pulmonary tuberculosis(resistance rates of RFP were 17.31％,IN H 13.46 ％,PZA 11.54 ％,EMB 10.58 ％,SM 9.62 ％),RFP resistance rate of HIV/TB infected patients was lower(P＜0.05).There was no significant difference between two groups in the other four anti-tuberculosis drug(P＞0.05).The coincidence rate with the absolute concentration method were INH 96.4％,RFP 98.2％,PZA 96.4％,EMB 93.8％ and SM 96.4％,respectively.Conclusion The resistance rate of mycobacterium tuberculosis to RFP in patients with HIV/TB infection in this region is lower than that in patients with common pulmonary tuberculosis,which is related to the good medication compliance of these patients.PhaB has the characteristic of fast,simple,without special equipment,it can be used as a rapid screening of mycobacterium tuberculosis drug resistance method.

Determining parameter distribution in within-host severe P. falciparum malaria.

Numerous studies have been carried out on within-host Plasmodium falciparum malaria with varying results. Some studies have suggested over estimation of parasite growth within an infected host while others stated that evolution of parasitaemia seems to be quelled by parasite load. Various mathematical models have been designed to understand the dynamics of evolution of within-host malaria. The basic ingredient in most of the models is that the availability of uninfected red blood cells (RBCs) in which the parasite develops is a limiting factor in the propagation of the parasite population. We hypothesize that in severe malaria, due to parasite quest for survival and rapid multiplication, the vicious malaria parasite is sophisticated and can be absorbed in an already infected RBC and speeds up rapture rate. The study reviews the classical models of blood stage malaria and proposes a new model which incorporates double infection. Analysis of the model and parameter identifiability using Markov chain Monte Carlo (MCMC) are presented. MCMC uses distribution of parameters to study the model behavior instead of single points. Results indicate that most infected RBCs rupture quickly due to the disease instead. This may explain anemia in malaria patients and lack of uniformity of oscillations in within-host malaria. Therefore, more needs to be done as far as within-host malaria is concerned, to provide step by step evolution of malaria within a host.