The success of Mycobacterium tuberculosis (M. tuberculosis) as a pathogen is largely contributes to its ability to manipulate the host immune responses. The genome of M. tuberculosis encodes multiple immune-modulatory proteins, including several members of the multi-genic PE_PPE family. Despite of intense research, the roles of PE_PGRS proteins in mycobacterial pathogenesis remain elusive. The function of M. tuberculosis PE_PGRS41, characterized by an extended and unique C-terminal domain, was studied. Expression of PE_PGRS41 in Mycobacterium smegmatis, a non-pathogenic species intrinsically deficient of PE_PGRS, severely impaired the resistance of the recombinant to multiple stresses via altering the cell wall integrity. Macrophages infected by M. smegmatis harboring PE_PGRS41 decreased the production of TNF-α, IL-1β and IL-6. In addition, PE_PGRS41 boosted the survival of M. smegmatis within macrophage accompanied with enhanced cytotoxic cell death through inhibiting the cell apoptosis and autophagy. Taken together, these results implicate that PE_PGRS41 is a virulence factor of M. tuberculosis and sufficient to confer pathogenic properties to M. smegmatis.

BackgroundChina has ambitious to achieve significant reductions in HIV transmission and HIV-related mortality by adopting the World Health Organization's “Treat All” approach. Such a prevention strategy is needed future study on regional scale.MethodsAn observational cohort study of HIV epidemiology and treatment databases was used to study the effectiveness of antiretroviral therapy on the transmission of HIV in serodiscordant couples in Guangxi of China.ResultsA total of 7713 couples were entered into the cohort study analysis which included 1885 couples in the treatment-naive cohort and 5828 couples in the treated cohort. During the follow-up of 18985.29 person-years from 2003 to 2014, the average incidence of HIV was 2.4 per 100 person-years (95% CI 2.1–2.6). HIV seroincidence rate was significantly higher among the treatment naive group (4.2 per 100 person-years, 3.7–4.8) compared with the on treatment group (1.6 per 100 person-years, 1.3–1.8). An overall 45% reduction in risk of HIV transmission among serodiscordant couple was associated with ART treatment (adjusted Hazard Ratio [HR] 0.55, 95% Confidence Interval [CI] 0.44–0.69). Treatment prevention had significantly effectiveness for most baseline characteristics of index partners, such as for male, female, age above 25 years, education below high school, farmer, infected by heterosexual intercourse.ConclusionTreatment-as-prevention can be implemented in the real-world on a national or regional scale, but ART adherence and comprehensive harm reduction while implementing this strategy require further study.

The aim of this review is to describe long-term HIV epidemiology and prevention trends in Guangxi, a provincial-level region located along a major drug trafficking corridor in southwestern China. Between 1996 and 2006, HIV transmission in Guangxi was primarily fueled by Injection Drug Use (IDU). Since 2006, heterosexual sex has become the dominant mode of HIV transmission, followed by drug injection. Moreover, older, heterosexual adults appear to be at increased risk for HIV. The vast majority of new HIV cases are attributed to local HIV subtypes already circulating within Guangxi (93%), though imported subtypes are associated with younger age groups. Since 2011, HIV incidence in Guangxi has stabilized, due in part to HIV prevention efforts that include expanded HIV testing, antiretroviral treatment, and other intervention measures. Between 1996 and 2017, Guangxi, China experienced dramatic changes in the primary HIV transmission mode and at-risk age group. Due in part to local and National AIDS control and prevention campaigns, HIV incidence trends in Guangxi no longer appear to be increasing.

Mycobacterium tuberculosis PE/PPE family proteins, named after the presence of conserved PE (Pro-Glu) and PPE (Pro-Pro-Glu) domains at N-terminal, are prevalent in M. tuberculosis genome. The function of most PE/PPE family proteins remains elusive. To characterize the function of PE_PGRS18, the encoding gene was heterologously expressed in M. smegmatis, a nonpathogenic mycobacterium. The recombinant PE_PGRS18 is cell wall associated. M. smegmatis PE_PGRS18 recombinant showed differential response to stresses and altered the production of host cytokines IL-6, IL-1β, IL-12p40 and IL-10, as well as enhanced survival within macrophages largely via attenuating the apoptosis of macrophages. In summary, the study firstly unveiled the role of PE_PGRS18 in physiology and pathogenesis of mycobacterium.

Tuberculosis, caused by Mycobacterium tuberculosis (MTB) infection, remains a grave global public health burden which claims the lives around two to three million annually. PE and PPE proteins, featured by the Pro-Glu (PE) or Pro-Pro-Glu (PPE) motifs at the conserved N-terminal domain, are abundant in the MTB genome. PPE32 can increase intracellular survival of mycobacteria through abnormally increase in cytokines production. PPE32 might subvert the macrophage immune response and thwart its bactericidal effect. THP-1 macrophages treated with PPE32 or infected with Mycobacterium smegmatis (MS) expression PPE32 showed increase of cytokines production and multiple hallmarks of apoptosis. We found that PPE32 significantly increases the expression of IL-12p40 and IL-32 through ERK1/2 signaling pathway. In addition, the cell viability of macrophage was inhibited after PPE32 stimulation. We noted that PPE32 induces cleavage of caspase-3 and caspase-9, while inhibition of caspase activity significantly abrogates the PPE32-induced cell apoptosis. Moreover, PPE32 treatment promotes endoplasmic reticulum stress related gene expression, suggesting ER stress might be responsible for PPE32-induced cell apoptosis.