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Brucellosis is a zoonotic and contagious infectious disease caused by Brucella spp, which causes substantial economic losses to animal husbandry and leads to severe public health problems. Brucella have evolved multiple strategies to escape host immunity and survive within host cells. Elucidating the immune evasion strategies during Brucella infection will facilitate the control of brucellosis. The host enzyme, heme oxygenase‐1 (HO‐1), is a multifunctional protein that functions during inflammatory diseases and microbial infections. However, how HO‐1 functions during Brucella infection is rarely studied. In this study, we evaluated the role of HO‐1 during Brucella infection. We found that Brucella infection induced HO‐1 expression in macrophages. We further showed that HO‐1 was regulated by PI3K, AMPK kinase, and nuclear erythroid‐related factor 2 (Nrf2) in macrophages. Interestingly, knocking out HO‐1 or inhibiting the activity of HO‐1 significantly decreased Brucella intracellular growth. Inducing the expression of HO‐1 by treatment with CoPP promoted Brucella intracellular growth. Mechanistic analyses indicated that the effect of HO‐1 was not meditated by HO‐1 metabolites, but by decreasing the production of reactive oxygen species (ROS), TNF‐α, and IL‐1β. Moreover, Brucella induced HO‐1 expression in bone marrow‐derived macrophages (BMDMs) and mice. When the expression of HO‐1 was knocked down in BMDMs, the intracellular survival of Brucella was reduced. Furthermore, the induction of HO‐1 by CoPP significantly increased bacterial loads in vivo. Thus, we demonstrated that Brucella induced HO‐1 expression to promote its survival and growth in vitro and in vivo. This study also identified HO‐1 as a novel innate immune evasion factor during Brucella infection. [ABSTRACT FROM AUTHOR]

The novel coronavirus disease (COVID‐19) poses a serious threat to global public health and economics. Serial interval (SI), time between the onset of symptoms of a primary case and a secondary case, is a key epidemiological parameter. We estimated SI of COVID‐19 in Shenzhen, China based on 27 records of transmission chains. We adopted three parametric models: Weibull, lognormal and gamma distributions, and an interval‐censored likelihood framework. The three models were compared using the corrected Akaike information criterion (AICc). We also fitted the epidemic curve of COVID‐19 to the logistic growth model to estimate the reproduction number. Using a Weibull distribution, we estimated the mean SI to be 5.9 days (95% CI: 3.9–9.6) with a standard deviation (SD) of 4.8 days (95% CI: 3.1–10.1). Using a logistic growth model, we estimated the basic reproduction number in Shenzhen to be 2.6 (95% CI: 2.4–2.8). The SI of COVID‐19 is relatively shorter than that of SARS and MERS, the other two betacoronavirus diseases, which suggests the iteration of the transmission may be rapid. Thus, it is crucial to isolate close contacts promptly to effectively control the spread of COVID‐19. [ABSTRACT FROM AUTHOR]

Brucellosis is an important zoonotic disease worldwide, caused by Brucella spp., which are facultative intracellular bacteria with no classic virulence factors, as virulence is dependent on the ability to invade and replicate within host cells. In this study, we identified a novel gene bab_RS22045 that encodes a small highly conserved protein in Rhizobiales. To investigate the role of this gene, a deletion mutant and complement strain were constructed. Virulence testing showed that bab_RS22045 is necessary for Brucella virulence, and was designated as virulence‐related hypothetical protein, VhpA. The results of a cell infection experiment showed that vhpA was not associated with Brucella adherence to and invasion of HeLa cells, or further intracellular survival within RAW264.7 cells. The results of sensitivity testing showed the vhpA mutant had similar sensitivity to hydrogen peroxide, polymyxin B, and sodium nitroprusside as the wild‐type (WT) strain. Interestingly, RNA‐seq analysis showed that deletion of the vhpA gene affected the expression patterns of multiple Brucella genes, and the main four up‐regulated genes and five down‐regulated genes were further confirmed using quantitative real‐time PCR analysis. Subsequently, a series of over‐expression strains were constructed, and virulence testing showed that over‐expression of four up‐regulated genes (bab_RS17930, bab_RS17925, bab_RS26460, and bab_RS30050) significantly reduced virulence of the WT strain, and over‐expression of bab_RS18680 in the vhpA mutant partially restored virulence, suggesting that vhpA plays an important role in Brucella virulence by changing the expression patterns of multiple genes. Additionally, heterogeneous complementary analysis showed that the homologous vhpA genes of Sinorhizobium meliloti and Agrobacterium tumefaciens could not restore virulence of the vhpA mutant, although VhpA is a highly conserved protein in Rhizobiales. Overall, a novel, small, hypothetical gene was identified that is associated with B. abortus virulence, which highlights the roles of small encoding genes in Brucella virulence. [ABSTRACT FROM AUTHOR]