ISSN 1673-6184 CN 31-1966/R
The combined antiretroviral therapy (cART) has been applied to control the course of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). However, cART requires lifelong daily treatment and strict adherence. HIV can quickly rebound after drug withdrawal because of the presence of the latent HIV reservoir in vivo. Therefore, reactivation of latent HIV and elimination of latent HIV reservoir are critical for cure of HIV infection and AIDS. Here, we review the recent advancements and future prospects on the strategies for HIV cure.
Human immunodeficiency virus (HIV) infection is a risk factor for invasive fungal infections (IFIs). IFI remains one of the major opportunistic infections and a leading cause of infection-related mortality in HIV/acquired immunodeficiency syndrome (AIDS) patients in spite of the widespread use of highly active antiretroviral therapy (HAART). The most common IFIs include mucocutaneous candidiasis, pneumocystis pneumonia, cryptococcal meningitis, and penicilliosis marneffei. Compared with non-HIV infection patients, the diagnosis of IFI in HIV patients is more complex and special. Diagnosis should be made through the combined analysis of the immune status of the patients, clinical manifestations, imaging examinations and mycological laboratory test results. The diagnostic methodology for IFI in non-HIV patients should not be simply applied in HIV patients, and the sensitivity and specificity of some diagnostic techniques should be re-evaluted in HIV patients. Antifungal therapy and HAART are the two essential aspects of the treatment of HIV coinfection with IFIs. Careful attention should be paid to drug interactions between antifungal agents and HAART. HIV patients who have completed the initial antifungal therapy should be administered chronic maintenance therapy with antifungal drugs according to CD4 cell counts, drug-drug interactions and side effects. HIV patients are highly vulnerable to IFIs, and chemoprophylaxis for high-risk patients with severe immunosuppression should be initiated to decrease the incidence of special IFIs in HIV patients. Early diagnosis and optimized treatment for IFIs in HIV patients need to be further studied and explored.
To investigate Clostridium difficile (C. difficile)associated diarrhea (CDAD) in human immunodeficiency virus (HIV)infected inpatients in Shanghai, C. difficile and general intestinal tract pathogenic bacteria were isolated by selective medium from abnormal fecal specimens collected from 250 HIV infected inpatients from March 2012 to March 2013. The susceptibilities of C. difficile to metronidazole, vancomycin, clindamycin and moxifloxacin were determined by E-test method. Molecular typing was performed by multilocus sequence typing (MLST). The genes tcdA and tcdB of toxins A and B were detected by conventional polymerase chain reaction (PCR). 29 clinical strains of C. difficile were isolated from 250 fecal specimens (11.6%), in which 17 strains were tcdA＋/tcdB＋ and 12 strains were tcdA－/tcdB－. All strains were susceptible to metronidazole and vancomycin. Resistance to clindamycin and moxifloxacin was found in 69.0% and 31.0% strains respectively. A total of 12 different sequence types (ST2, 3, 7, 8, 26, 35, 37, 38, 39, 54, 81, and 124) were identified. The most prevalent ST types were ST54 (6/29, 20.7%) and ST39 (5/29, 17.2%). The results suggest that the rate of positive C. difficile detection is high and should be monitored strictly to prevent outbreak.
This study aims to investigate the epidemiology of human cytomegalovirus (HCMV) among pregnant women and hospitalized children in central China area, and to evaluate the value of different samples 〔breast milk, urine and peripheral blood mononuclear cells (PBMCs)〕 for diagnosis of HCMV infection. HCMVspecific IgM and IgG antibodies were determined by electrochemiluminescence immunoassay to verify the infection status of HCMV. DNA isolated from different samples was subjected for the detection of HCMV specific gene(s) by realtime fluorescence quantitative polymerase chain reaction (PCR). For pregnant women and hospitalized children, the positive rate of IgM was 1.16% and 8.13% respectively. The rates for newborns and preterm infants were 2.06% and 3.50%. The positive rates of IgG for HCMV among pregnant women and hospitalized children were 96.59% and 79.98%, respectively, while the rates among newborns and preterm infants were 83.84% and 94.59%, respectively. The positive rates of HCMV DNA detection were 57.25% and 7.97% for urine and PBMCs, respectively (P<0.001). 44.61% of mothers shed HCMV DNA in breast milk, while 0.77% were found positive in PBMCs (P<0.001). The results suggest that HCMV infection rate in pregnant women is considerably high and HCMV is one of the pathogens for hospitalized children infection. The preterm infants seem more sensitive to HCMV infection than the term infants, and the analysis of the presence of viral DNA from urine in hospitalized children is more suitable for the diagnosis of HCMV infection. HCMV DNA has a higher positive rate in breast milk than in PBMCs from lactating mothers and maternal milk is the main source for HCMV transmission from mother to infant.
A novel DNA vaccine pFUW-Ag85B-Rv3425 based on lentiviral vector pFUW was constructed to improve the transfection efficiency in vivo. The DNA injection combined with electroporation in C57BL/6 mice three times with two-week interval was conducted. After the last immunization, the mice were sacrificed. The spleen lymphocytes were isolated and analyzed by flow cytometry. The expression levels of IgG, IgG1, IgG2a, and interleukin 2 (IL-2) in serum were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that DNA injection in combination with electroporation could induce stronger humoral immunity, more Th1-type immune response and significantly enhance CD8+ T cell and CD27+ B cell proliferation. It is indicated that DNA vaccine in combination with electroporation can be taken as a new therapy strategy against tuberculosis.
The application of effective disinfectants during experimental activities of highpathogenic microorganism is crucial for decontamination of laboratory environment to prevent laboratoryacquired infections. In this study, the quantitative germicidal disinfectant validation experiments using membrane filtration suspension were conducted against Mycobacterium tuberculosis (M. tuberculosis) H37Rv. Sodium hypochlorite solution (containing 1 000 mg/L active chlorine), 75% ethanol/water, and Safespore disinfectant killed M. tuberculosis efficiently. When the concentration of ethanol decreased to 37.5%, it was still able to kill M. tuberculosis by prolonging killing time to 10 min. The results suggest that 75% ethanol/water is suitable as conventional disinfectant and sodium hypochlorite solution (containing 1 000 mg/L active chlorine) is suitable under emergency and accident in biosafety level 3 laboratories (BSL3)．
To study the role of polymerase chain reaction-high-resolution melt (PCR-HRM) in the detection of mixed bacteria from respiratory tract, the fluid from the lower respiratory tract of patients with chronic obstructive pulmonary disease (COPD) was collected through bronchoscopy. Total DNA of bacteria was extracted and the full-length 16S rDNA was amplified by PCR with 16S primers 27F/1492R. PCR products were electrophoresed and purified, and then connected to pGEMT-Easy carrier to build 16S rDNA clone library. The cloned library was amplified by 338F/518R (16S rDNA-V3 region universal primer). PCR-HRM in V3 region was performed by Roche LightCycler 480 real-time fluorescence quantitative PCR system. The data were analyzed by HRM GeneScan analysis software. According to the different HRM patterns, clonal strains were selected for sequencing to identify bacterial strain. The results showed that PCR-HRM could be responsive to distinguish the 16S rDNA-V3 regions from different bacteria of the lower respiratory tract and cloned strain sequencing sample size was significantly reduced according to HRM patterns. PCR-HRM technology can be used as a rapid, high-throughput, sensitive and economic detection method of bacterial diversity.
Hand, foot and mouth disease (HFMD) is a common acute infectious disease caused by enteroviruses, whose most common pathogens are human enterovirus 71 and coxsackievirus A16. Coxsackievirus A6 is relatively rare. Here a rare HFMD case complicated with systemic herpes and cervical spinal cord involved is reported. The rashes caused by HFMD were most commonly seen at the palm of hand and foot, hip, knee and elbow joint. The infant was developed to systemic herpes quickly and complicated with significantly increased neuron specific enolase and imaging changes of cervical spinal cord in magnetic resonance imaging (MRI). Under the treatment of anti-inflammatory, anti-virus, and supporting therapy, the systemic herpes disappeared and the infant fully recovered. Clinical physicians should paid more attention to this rare case caused by coxsackievirus A6.
microRNA (miRNA) is a class of small non-coding RNA with the length of 18-25 nucleotides, which plays an important role in regulating posttranscriptional level of genes through binding to 3’-untranslated region (UTR) of mRNA. Given its involvement in the development of various human diseases, miRNAs are increasingly becoming new generation biomarkers for diagnosis and prognosis, as well as novel therapeutic targets. The disease progression of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) might be modified by miRNA through regulating the viral replication or host immune responses induced by HIV-1 infection. Here, the progresses on host miRNAs as potential biomarkers of disease progression in HIV-1 infection, as well as potential targets for antiretroviral therapy are reviewed in the present paper.
Acquired immunodeficiency syndrome (AIDS), still a serious infectious disease, causes global epidemic and remains incurable until now. The current available antiretroviral therapy successfully inhibits human immunodeficiency virus (HIV) replication, but can not eradicate the genome-integrated HIV. Recently, genome editing techniques, such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) (CRISPR-Cas system), have been found to successfully disrupt the integrated HIV-1 genes. Furthermore, genome editing techniques also have successfully induced C-C chemokine receptor type 5 (CCR5) ?32 mutation, a mutation of HIV entry coreceptor CCR5 that is resistant to HIV infection. Therefore, genome editing techniques bring the glimmers of success in eradication of HIV in human bodies.
