BackgroundLong-term antibody responses to 23-valent pneumococcal polysaccharide vaccine (PPV) among HIV-infected patients receiving highly active antiretroviral therapy (HAART) are rarely investigated. MethodsAntibody responses to three pneumococcal capsular polysaccharides [Pneumococcal polysaccharide (PPS) 14, 19F and 23F] were assessed among 169 HIV-infected patients who received HAART and 23-valent PPV. Patients were stratified into four groups according to CD4 count at vaccination: group 1, CD4o100 cells/mL (n 5 35); group 2, CD4 100-199 cells/mL (n 5 36); group 3, CD4 200-349 cells/mL (n 5 34); and group 4, CD4 ! 350 cells/mL (n 5 64). The proportion of patients who achieved increases in antibody titres of twofold or greater from baseline values (responders) was compared among the four groups of patients for five consecutive years after vaccination. ResultsThe proportion of responders to the three serotypes was significantly lower among patients in group 1 compared with those in the other three groups during yearly follow-up. Much faster loss of antibody responses was observed in group 1, although the rate of decline varied with the serotypes studied in the four groups. Compared with the nonresponders, more responders had CD4 counts 4100 cells/mL at vaccination and achieved better virological suppression throughout the 5-year period, while the absolute increases of CD4 cell counts after HAART were not statistically significantly different. ConclusionsDespite continued increases in CD4 cell counts after HAART, the proportion of HIV-infected patients who maintained antibody responses to PPV declined significantly over the 5-year follow-up period, especially among those who had CD4 counts o100 cells/mL at vaccination and who failed to achieve virological suppression. DOI: 10.1111/j.1468-1293.2009.00744.x HIV Medicine (2010 r 2009 British HIV Association 54 antiretroviral therapy (HAART) [1]. Although cohort or population-based surveillance studies suggest that the incidence of invasive pneumococcal infections or pneumococcal pneumonia declines among HIV-infected patients with access to HAART and appropriate antimicrobial prophylaxis [2,4,6,7], it remains significantly higher among HIV-infected patients than in the general population, with risk ratios ranging from 35 to 60 [2][3][4]. In observational studies conducted in several developed countries, vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV) has been shown to decrease the risk of invasive pneumococcal infections among HIVinfected patients [5,[8][9][10][11][12]. According to U.S. Public Health Service/Infectious Diseases Society of America (USPHS/ IDSA) guidelines, it is recommended that patients with HIV infection who have CD4 lymphocyte counts of 4200 cells/mL should receive 23-valent PPV, and revaccination can be considered for those patients who have initial CD4 counts of o200 cells/mL and whose CD4 counts increase to ! 200 cells/mL after receipt of HAART and for those patients who have undergone pneumococcal polysaccharide v...

The pandemic outbreak of a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has threatened the global public health and economy since late December 2019. SARS-CoV-2 encodes the conserved macro domain within nonstructural protein 3, which may reverse cellular ADP-ribosylation and potentially cut the signal of a viral infection in the cell. Herein, we report that the SARS-CoV-2 macro domain was examined as a poly-ADP-ribose (ADPR) binding module and possessed mono-ADPR cleavage enzyme activity. After confirming the ADPR binding ability via a biophysical approach, the X-ray crystal structure of the SARS-CoV-2 macro domain was determined and structurally compared with those of other viruses. This study provides structural, biophysical, and biochemical bases to further evaluate the role of the SARS-CoV-2 macro domain in the host response via ADP-ribose binding but also as a potential target for drug design against COVID-19.

PrtA is an extracellular serine protease of Vibrio parahaemolyticus and has haemolytic and cytotoxic activities. Many extracellular proteases have been shown to be required for nutrient intake and the infection mechanism of vibrios. In this study, we report that OpaR, a quorum sensing regulator, and RpoS, a general stress response regulator, play important roles in the PrtA regulation pathway. Extracellular protease activity was highest during the late-log growth of Vibrio parahaemolyticus no.93 (VP93). The absence of PrtA distinctly decreased the extracellular protease activity. Deletion of opaR or rpoS alone reduced PrtA-specific activity of VP93. Quantitative reverse-transcriptase PCR and Western blot analysis suggested that OpaR and RpoS promote PrtA expression at the transcriptional level and affect the amount of extracellular PrtA. A luciferase assay revealed that OpaR regulates prtA on the prtA promoter region. Electrophoretic mobility shift assays indicated that the purified His-OpaR was able to bind specifically to two sequences (PrtA-1 and PrtA-2) of the prtA promoter region. Footprinting analysis showed that OpaR regulates prtA by binding to the promoter region of prtA at positions -269 to -246 and -88 to -68 from the prtA translational start site. Together, the results suggest that PrtA was upregulated by two global regulators, OpaR and RpoS.

Proteases play a key role in numerous bacterial physiological events. Microbial proteases are used in the pharmaceutical industry and in biomedical applications. The genus Vibrio comprises protease-producing bacteria. Proteases transform polypeptides into shorter chains for easier utilization. They also function as a virulence factor in pathogens. The mechanism by which protease genes are regulated in Vibrio parahaemolyticus, an emerging worldwide human pathogen, however, still remains unclear. Quorum sensing is the communication system of bacteria. OpaR is the master quorumsensing regulator in V. parahaemolyticus. In the present study, quantitative reverse transcriptase-polymerase chain reaction and protease gene promoter-fusion reporter assays revealed that OpaR represses seven protease genes-three metalloprotease genes and four serine protease genes-which are involved in environmental survival and bacterial virulence. Furthermore, the electrophoresis mobility shift assay demonstrated that OpaR is bound directly to the promoter region of each of the seven protease genes. DNase I footprinting identified the sequence of these OpaR-binding sites. ChIPseq analyses revealed 435 and 835 OpaR-binding sites in the late-log and stationary phases, respectively. These OpaR-binding sequences indicated a conserved OpaRbinding motif: TATTGATAAAATTATCAATA. These results advance our understanding of the protease regulation system in V. parahaemolyticus. This study is the first to reveal the OpaR motif within V. parahaemolyticus in vivo, using ChIP-seq, and to provide a database for OpaR direct regulon.

No abstract