Soybean-derived Bowman-Birk Inhibitor (BBI) Inhibits HIV Replication in Macrophages.

The Bowman-Birk inhibitor (BBI), a soybean-derived protease inhibitor, is known to have anti-inflammatory effect in both in vitro and in vivo systems. Macrophages play a key role in inflammation and immune activation, which is implicated in HIV disease progression. Here, we investigated the effect of BBI on HIV infection of peripheral blood monocyte-derived macrophages. We demonstrated that BBI could potently inhibit HIV replication in macrophages without cytotoxicity. Investigation of the mechanism(s) of BBI action on HIV showed that BBI induced the expression of IFN-ß and multiple IFN stimulated genes (ISGs), including Myxovirus resistance protein 2 (Mx2), 2',5'-oligoadenylate synthetase (OAS-1), Virus inhibitory protein (viperin), ISG15 and ISG56. BBI treatment of macrophages also increased the expression of several known HIV restriction factors, including APOBEC3F, APOBEC3G and tetherin. Furthermore, BBI enhanced the phosphorylation of IRF3, a key regulator of IFN-ß. The inhibition of IFN-ß pathway by the neutralization antibody to type I IFN receptor (Anti-IFNAR) abolished BBI-mediated induction of the anti-HIV factors and inhibition of HIV in macrophages. These findings that BBI could activate IFN-ß-mediated signaling pathway, initialize the intracellular innate immunity in macrophages and potently inhibit HIV at multiple steps of viral replication cycle indicate the necessity to further investigate BBI as an alternative and cost-effective anti-HIV natural product.

SIV Infection Facilitates Mycobacterium tuberculosis Infection of Rhesus Macaques.

Tuberculosis (TB) is a common opportunistic infection and the leading cause of death for human immunodeficiency virus (HIV)-infected patients. Thus, it is necessary to understand the pathogenetic interactions between M.tb and HIV infection. In this study, we examined M.tb and/or simian immunodeficiency virus (SIV) infection of Chinese rhesus macaques. While there was little evidence that M.tb enhanced SIV infection of macaques, SIV could facilitate M.tb infection as demonstrated by X-rays, pathological and microbiological findings. Chest X-rays showed that co-infected animals had disseminated lesions in both left and right lungs, while M.tb mono-infected animals displayed the lesions only in right lungs. Necropsy of co-infected animals revealed a disseminated M.tb infection not only in the lungs but also in the extrapulmonary organs including spleen, pancreas, liver, kidney, and heart. The bacterial counts in the lungs, the bronchial lymph nodes, and the extrapulmonary organs of co-infected animals were significantly higher than those of M.tb mono-infected animals. The mechanistic studies demonstrated that two of three co-infected animals had lower levels of M.tb specific IFN-γ and IL-22 in PBMCs than M.tb mono-infected animals. These findings suggest that Chinese rhesus macaque is a suitable and alternative non-human primate model for SIV/M.tb coinfection studies. The impairment of the specific anti-TB immunity is likely to be a contributor of SIV-mediated enhancement M.tb infection.

[Epidemiological characteristics of influenza virus and respiratory syncytial virus among children in Wuhan area from 2008 to 2012].

OBJECTIVE: To investigate the infection status and epidemiological characteristics of influenza virus and respiratory syncytial virus (RSV) in influenza-like illness (ILI) of children ( ≤ 14 years) in Wuhan area from 2008 to 2012. METHODS: A total of 2854 cases of ILI patients ( ≤ 14 years) in a hospital of Wuhan were recruited in the study from July 2008 to June 2012. The sample of pharyngeal swab was collected from each patient, to extract the virus nucleic acids. Real-time fluorescent quantitation reverse transcription PCR (RT-PCR) method was applied to detect the subtypes of influenza virus and RSV, and then analyzed the time and age characteristics. RESULTS: Out of the 2854 cases, 758 (26.6%) were positive for influenza virus,including 547 (19.2%) influenza A virus positive samples and 211 (7.4%) influenza B virus positive samples. Usually, there were two peaks present in the annual curve of influenza virus, namely summer peak and winter/spring peak. The positive rate of influenza virus in 6-14 years old children (48.0%, 275/573) was significantly higher than that in 3-5 years old children (26.6%, 213/801) and that under 3 years old children (18.3%, 270/1480). The difference showed statistical significance (χ(2) = 187.432, P < 0.01). A total of 219 (7.7%) cases were positive for RSV,including 108 RSV-A positive samples and 112 RSV-B positive samples (1 co-infection). The epidemic of RSV showed an obvious seasonal pattern with peaks in autumn,winter and spring,which accounted for 96.8% (212/219) of all the cases; however, the annual incidence of RSV fluctuated greatly. The predominant subtype shifted every 2 years. RSV-B predominated during September 2008 and May 2009, December 2009 and March 2010, accounting for 76.6% (36/47) and 96.9% (62/64) respectively. RSV-A predominated during November 2010 and March 2011, September 2011 and April 2012, accounting for 92.5% (37/40) and 100.0% (48/48) respectively. With the increase of the age, the positive rate of RSV-A and RSV-B decreased gradually (RSV-A: χ(2) = 36.223, P < 0.01; RSV-B: χ(2) = 36.281, P < 0.01). The positive rates of RSV-A in children < 1,1,2,3,4,5-9 and 10-14 years old were 7.0% (26/373), 5.9% (39/662), 4.0% (18/445), 3.2% (13/406), 1.3% (3/236), 1.4% (7/517) and 0.9% (2/215) respectively; while, the positive rates of RSV-B in each age group were 6.4% (24/373), 6.0% (40/662), 4.5% (20/445), 4.4% (18/406), 1.3% (3/236), 1.0% (5/517) and 0.9% (2/215) respectively. The children aged 0-3 years old were more susceptible for RSV infection,accounting for 90.0% (197/219) of the total positive samples. During the outbreak of influenza A H1N1 in November 2009, the positive rate of RSW was 3.0% (3/100), lower than that in the same month of 2008, 2010 and 2011,which were separately 18.2% (6/33), 10.8% (10/93) and 10.0% (4/40). The difference showed statistical significance (χ(2) = 8.450, P < 0.05). During the outbreak of influenza A (H1N1) in January 2011,the positive rate of RSV was 5.7% (3/53), lower than those in the same month of 2009, 2010 and 2012, which was separately 21.7% (5/23), 28.6% (22/77) and 16.0% (8/50). The difference showed statistical significance (χ(2) = 11.233,P < 0.05). During the period of less influenza happened in September 2011, the RSV positive rate was 25.0% (10/40), higher than those in the same month of 2008, 2009 and 2010, which was separately 11.4% (4/35), 1.7% (2/118) and 0.0% (0/109). The difference showed statistical significance (χ(2) = 32.521, P < 0.01). CONCLUSION: Both influenza virus and RSV were important etiological agents of ILI of children in Wuhan. The characteristics of seasonal and age distributions of the two viruses were notably different; meanwhile, a certain inhibitional effect of influenza virus on RSV could be observed.