Arsenic trioxide-induced apoptosis contributes to suppression of viral reservoir in SIV-infected rhesus macaques.

Latent viral reservoir is recognized as the major obstacle to achieving a functional cure for HIV infection. We previously reported that arsenic trioxide (AsO) combined with antiretroviral therapy (ART) can reactivate the viral reservoir and delay viral rebound after ART interruption in chronically simian immunodeficiency virus (SIV)-infected macaques. In this study, we further investigated the effect of AsO independent of ART in chronically SIV-infected macaques.

Rational design of AAVrh10-vectored ACE2 functional domain to broadly block the cell entry of SARS-CoV-2 variants.

The frequently emerging SARS-CoV-2 variants have weakened the effectiveness of existing COVID-19 vaccines and neutralizing antibody therapy. Nevertheless, the infections of SARS-CoV-2 variants still depend on angiotensin-converting enzyme 2 (ACE2) receptor-mediated cell entry, and thus the soluble human ACE2 (shACE2) is a potential decoy for broadly blocking SARS-CoV-2 variants. In this study, we firstly generated the recombinant AAVrh10-vectored shACE2 constructs, a kind of adeno-associated virus (AAV) serotype with pulmonary tissue tropism, and then validated its inhibition capacity against SARS-CoV-2 infection.

Comparison of the Immunogenicity of HIV-1 CRF07_BC Gag Antigen With or Without a Seven Amino Acid Deletion in p6 Region.

HIV-1 CRF07_BC-p6Δ7, a strain with a seven amino acid deletion in the p6 region of the Gag protein, is becoming the dominant strain of HIV transmission among men who have sex with men (MSM) in China. Previous studies demonstrated that HIV-1 patients infected by CRF07_BC-p6Δ7 strain had lower viral load and slower disease progression than those patients infected with CRF07_BC wild-type strain. However, the underlying mechanism for this observation is not fully clarified yet.

Acylated homoserine lactones regulate the response of methane metabolism and nitrogen metabolism to florfenicol in anaerobic fermentation.

Antimicrobial agents enter the ecological environment through animal excreta and disrupt metabolism in environmental microorganisms. Quorum sensing (QS) can help bacteria adapt to their surroundings. To explore how acyl-homoserine lactone (AHL) can adjust the influence of florfenicol on nitrogen cycling and methane metabolism in anaerobic fermentation, a small indoor thermostatic anaerobic fermentation model was established by adding exogenous acylated homoserine lactone (AHL) signal molecules with florfenicol as the stress factor.

Strategies to Develop a Mucosa-Targeting Vaccine against Emerging Infectious Diseases.

Numerous pathogenic microbes, including viruses, bacteria, and fungi, usually infect the host through the mucosal surfaces of the respiratory tract, gastrointestinal tract, and reproductive tract. The mucosa is well known to provide the first line of host defense against pathogen entry by physical, chemical, biological, and immunological barriers, and therefore, mucosa-targeting vaccination is emerging as a promising strategy for conferring superior protection. However, there are still many challenges to be solved to develop an effective mucosal vaccine, such as poor adhesion to the mucosal surface, insufficient uptake to break through the mucus, and the difficulty in avoiding strong degradation through the gastrointestinal tract.

Killing Two Birds with One Stone by Administration of Soluble ACE2: A Promising Strategy to Treat Both Cardiovascular Diseases and SARS-CoV-2 Infection.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells mainly by the angiotensin converting enzyme 2 (ACE2) receptor, which can recognize the spike (S) protein by its extracellular domain. Previously, recombinant soluble ACE2 (sACE2) has been clinically used as a therapeutic treatment for cardiovascular diseases. Recent data demonstrated that sACE2 can also be exploited as a decoy to effectively inhibit the cell entry of SARS-CoV-2, through blocking SARS-CoV-2 binding to membrane-anchored ACE2.

Exacerbated AIDS Progression by PD-1 Blockade during Therapeutic Vaccination in Chronically Simian Immunodeficiency Virus-Infected Rhesus Macaques after Interruption of Antiretroviral Therapy.

The persistence of cells latently infected with HIV-1, named the latent reservoir, is the major barrier to HIV-1 eradication, and the formation and maintenance of the latent reservoir might be exacerbated by activation of the immunoinhibitory pathway and dysfunction of CD8 T cells during HIV-1 infection. Our previous findings demonstrated that prophylactic vaccination combined with PD-1 blockade generated distinct immune response profiles and conferred effective control of highly pathogenic SIV infection in rhesus macaques. However, to our surprise, herein we found that a therapeutic vaccination in combination with PD-1 blockade resulted in activation of the viral reservoir, faster viral rebound after treatment interruption, accelerated AIDS progression, and, ultimately, death in chronically SIV-infected macaques after antiretroviral therapy (ART) interruption.

Shell-mediated phagocytosis to reshape viral-vectored vaccine-induced immunity.

Adenovirus (Ad) has been extensively developed as a gene delivery vector, but the potential side effect caused by systematic immunization remains one major obstacle for its clinical application. Needle-free mucosal immunization with Ad-based vaccine shows advantages but still faces poor mucosal responses. We herein report that the chemical engineering of single live viral-based vaccine effectively modulated the location and pattern of the subsequently elicited immunity.

Safety of SARS-CoV-2 vaccines: a systematic review and meta-analysis of randomized controlled trials.

Background: Various modalities of vaccines against coronavirus disease 2019 (COVID-19), based on different platforms and immunization procedures, have been successively approved for marketing worldwide. A comprehensive review for clinical trials assessing the safety of COVID-19 vaccines is urgently needed to make an accurate judgment for mass vaccination.

Main Text: A systematic review and meta-analysis was conducted to determine the safety of COVID-19 vaccine candidates in randomized controlled trials (RCTs).

Modulation of Antiviral Immunity and Therapeutic Efficacy by 25-Hydroxycholesterol in Chronically SIV-Infected, ART-Treated Rhesus Macaques.

Cholesterol-25-hydroxylase (CH25H) and its enzymatic product 25-hydroxycholesterol (25HC) exert broadly antiviral activity including inhibiting HIV-1 infection. However, their antiviral immunity and therapeutic efficacy in a nonhuman primate model are unknown. Here, we report that the regimen of 25HC combined with antiretroviral therapy (ART), provides profound immunological modulation towards inhibiting viral replication in chronically SIV-infected rhesus macaques (RMs).

Impact of acyl-homoserine lactones on the response of nitrogen cycling in sediment to florfenicol stress.

Antibiotic residuals disrupt environmental microbial metabolism and can alter the nitrogen cycle. Quorum sensing has both inter- and intra-species effects that are directly related to the population densities necessary for microbial nitrogen cycling. Here, we explored how acyl-homoserine lactones (AHLs) can change the response of nitrogen cycling to florfenicol in sediments.

Broadly Antiviral Activities of TAP1 through Activating the TBK1-IRF3-Mediated Type I Interferon Production.

Deeply understanding the virus-host interaction is a prerequisite for developing effective anti-viral strategies. Traditionally, the transporter associated with antigen processing type 1 (TAP1) is critical for antigen presentation to regulate adaptive immunity. However, its role in controlling viral infections through modulating innate immune signaling is not yet fully understood.

An online survey of the attitude and willingness of Chinese adults to receive COVID-19 vaccination.

: A safe and effective vaccine against COVID-19 has become a public health priority. However, little is known about the public willingness to accept a future COVID-19 vaccine in China. This study aimed to understand the willingness and determinants for the acceptance of a COVID-19 vaccine among Chinese adults.

Effects of normal pregnancy on maternal EEG, TCD, and cerebral cortical volume.

Objective: Pregnancy causes many changes in our body and some of them may affect our ability of learning and memory. We examined the cerebral cortical volume of brain during pregnancy and measured changes in the brain electrical activity and cerebral blood flow.

Method: 35 women (20 normal full-term primigravida and 15 non-pregnant women) received the Electroencephalography (EEG) and Transcranial Doppler ultrasonography (TCD).

Arsenic Trioxide Impacts Viral Latency and Delays Viral Rebound after Termination of ART in Chronically SIV-Infected Macaques.

The latent viral reservoir is the source of viral rebound after interruption of antiretroviral therapy (ART) and is the major obstacle in eradicating the latent human immunodeficiency virus-1 (HIV-1). In this study, arsenic class of mineral, arsenic trioxide, clinically approved for treating acute promyelocytic leukemia, is demonstrated to reactivate latent provirus in CD4+ T cells from HIV-1 patients and Simian immunodeficiency virus (SIV)-infected macaques, without significant systemic T cell activation and inflammatory responses. In a proof-of-concept study using chronically SIVmac239-infected macaques, arsenic trioxide combined with ART delays viral rebound after ART termination, reduces the integrated SIV DNA copies in CD4+ T cells, and restores CD4+ T cells counts in vivo.

Preexisting Virus-Specific T Lymphocytes-Mediated Enhancement of Adenovirus Infections to Human Blood CD14+ Cells.

Antigen-specific T lymphocytes play a critical role in controlling viral infections. However, we report here that preexisting virus-specific T cell responses also contribute to promoting adenovirus (Ad) infection. Previously, we found that CD14+ monocytes from Ad-seropositive individuals exhibited an increased susceptibility to Ad infection, when compared with that of Ad-seronegative individuals.

Immune Protection of SIV Challenge by PD-1 Blockade During Vaccination in Rhesus Monkeys.

Though immune correlates for protection are still under investigation, potent cytotoxic T lymphocyte responses are desirable for an ideal HIV-1 vaccine. PD-1 blockade enhances SIV-specific CD8+ T cells. However, little information has been reported about how it affects the immunogenicity and protection of prophylactic SIV vaccines in nonhuman primates.

Structure-optimized dihydropyranoindole derivative GIBH-LRA002 potentially reactivated viral latency in primary CD4+ T lymphocytes of chronic HIV-1 patients.

Based on structure modification and a high-throughput Jurkat-Lat cell screening model, we found that GIBH-LRA002, ethyl-2-amino-3-cyano-9-methyl-4-(trifluoromethyl)-4,9-dihydropyrano[2,3-]indole-4-carboxylate, effectively reactivated the latent proviruses in a Jurkat-Lat cell line and primary CD4+ T cells from both chronic SIV-infected rhesus macaques and HIV-1 patients but without inducing systemic activation, making this compound attractive for potentially treating HIV-1 infection.

Scavenger receptor-mediated Ad5 entry and acLDL accumulation in monocytes/macrophages synergistically trigger innate responses against viral infection.

Adenovirus serotype 5 (Ad5) is a common cause of respiratory tract infection, and populations worldwide have high prevalence of anti-Ad5 antibodies, implying extensively prior infection. Ad5 infection potently activates the host innate defense and inflammation, but the molecular mechanisms are not completely clarified. We report here that monocytes from Ad5-seropositive subjects upregulates the expression of scavenger receptor A (SR-A), and the increased SR-A promote the susceptibility of Ad5 entry and subsequent innate signaling activation.