Novel role of host protein SLC25A42 in the HIV-1 reactivation of latent HIV-1 provirus.

Despite the effectiveness of combination antiretroviral therapy, human immunodeficiency virus (HIV) infection remains incurable. To seek new strategies to overcome HIV type 1 (HIV-1) latency, one of the major barriers to HIV elimination, it is crucial to better understand how this state is maintained. Here, by means of an RNA interference screen employing an HIV-1 latency model using monocytic cell lines, we identified solute carrier family 25 member 42 (SLC25A42) as a potential host factor not previously known to affect HIV-1 latency. SLC25A42 knockdown resulted in increased HIV-1 expression, whereas forced expression of exogenous SLC25A42 suppressed it in SLC25A42-depleted cells. SLC25A42 depletion increased HIV-1 proviral transcriptional elongation but did not cause HIV-1 activation in an HIV-1 Tat-depleted latency model. This suggests that the role of SLC25A42 in HIV-1 transcription depends on HIV-1 Tat. Chromatin immunoprecipitation-qPCR analysis further revealed that SLC25A42 accumulated on or near the HIV-1 5' long terminal repeat promoter region of the HIV-1 provirus, suggesting a possible role in regulating HIV-1 Tat near this promoter region. These results indicate that SLC25A42 plays a novel role in HIV-1 latency maintenance in monocytic HIV-1 reservoirs.

Nosocomial outbreak of SARS-CoV-2 in a hospital ward during the Omicron variant-dominant wave with a review of the relevant literature.

Clusters of nosocomial coronavirus disease 2019 (COVID-19) were reported globally during the recent pandemic. Unfortunately, these clusters negatively impacted inpatient morbidity, mortality, and hospital functions. Using epidemiological data and whole genome sequencing (WGS) of SARS-CoV-2, the present study investigated an outbreak of COVID-19 at a university hospital. Eight inpatients and 13 healthcare workers tested positive for SARS-CoV-2 during a one-month period. Whole genome sequencing (WGS) of the virus in 11 patients revealed that two variants of concern belonging to the Omicron sublineages, BA.2.3 and BA1.1.2, had caused the outbreak during a time when the proportion of the Omicron lineage in the community was changing. When variants of concern are undergoing mutation, a response to the outbreak should be made with multiple variants in mind, even in the absence of epidemiological data showing close contact or other potential vectors of infection, and awareness about infection prevention and control should be raised to safeguard patient safety.

Evidence of Helicobacter pylori heterogeneity in human stomachs by susceptibility testing and characterization of mutations in drug-resistant isolates.

Heterogeneity of Helicobacter pylori communities contributes to its pathogenicity and diverse clinical outcomes. We conducted drug-susceptibility tests using four antibiotics, clarithromycin (CLR), amoxicillin (AMX), metronidazole and sitafloxacin, to examine H. pylori population diversity. We also analyzed genes associated with resistance to CLR and AMX. We examined multiple isolates from 42 Japanese patients, including 28 patients in whom primary eradication with CLR and AMX had failed, and 14 treatment-naïve patients. We identified some patients with coexistence of drug resistant- and sensitive-isolates (drug-heteroR/S-patients). More than 60% of patients were drug-heteroR/S to all four drugs, indicating extensive heterogeneity. For the four drugs except AMX, the rates of drug-heteroR/S-patients were higher in treatment-naïve patients than in primary eradication-failure patients. In primary eradication-failure patients, isolates multi-resistant to all four drugs existed among other isolates. In primary eradication-failure drug-heteroR/S-patients, CLR- and AMX-resistant isolates were preferentially distributed to the corpus and antrum with different minimum inhibitory concentrations, respectively. We found two mutations in PBP1A, G591K and A480V, and analyzed these in recombinants to directly demonstrate their association with AMX resistance. Assessment of multiple isolates from different stomach regions will improve accurate assessment of H. pylori colonization status in the stomach.

HIV-Tocky system to visualize proviral expression dynamics.

Determinants of HIV-1 latency establishment are yet to be elucidated. HIV reservoir comprises a rare fraction of infected cells that can survive host and virus-mediated killing. In vitro reporter models so far offered a feasible means to inspect this population, but with limited capabilities to dissect provirus silencing dynamics. Here, we describe a new HIV reporter model, HIV-Timer of cell kinetics and activity (HIV-Tocky) with dual fluorescence spontaneous shifting to reveal provirus silencing and reactivation dynamics. This unique feature allows, for the first time, identifying two latent populations: a directly latent, and a recently silenced subset, with the latter having integration features suggestive of stable latency. Our proposed model can help address the heterogeneous nature of HIV reservoirs and offers new possibilities for evaluating eradication strategies.