TLR10 Senses HIV-1 Proteins and Significantly Enhances HIV-1 Infection

Toll-like receptors (TLRs) play a crucial role in innate immunity and provide a first line of host defense against invading pathogens. Of the identified human TLRs, TLR10 remains an orphan receptor whose ligands and functions are poorly understood. In the present study, we sought to evaluate the level of TLR10 expression in breast milk (BM) and explore its potential function in the context of HIV-1 infection. We evaluated HIV-1-infected (Nigerian: n = 40) and uninfected (Nigerian: n = 27; Canadian: n = 15) BM samples for TLR expression (i.e., TLR10, TLR2, and TLR1) and report here that HIV-1-infected BM from Nigerian women showed significantly higher levels of TLR10, TLR1, and TLR2 expression. Moreover, the level of TLR10 expression in HIV-1-infected BM was upregulated by over 100-fold compared to that from uninfected control women. In vitro studies using TZMbl cells demonstrated that TLR10 overexpression contributes to higher HIV-1 infection and proviral DNA integration. Conversely, TLR10 inhibition significantly decreased HIV-1 infection. Notably, HIV-1 gp41 was recognized as a TLR10 ligand, leading to the induction of IL-8 and NF-κBα activation. The identification of a TLR10 ligand and its involvement in HIV-1 infection enhances our current understanding of HIV-1 replication and may assist in the development of improved future therapeutic strategies

TLR10 Senses HIV-1 Proteins and Significantly Enhances HIV-1 Infection

Toll-like receptors (TLRs) play a crucial role in innate immunity and provide a first line of host defense against invading pathogens. Of the identified human TLRs, TLR10 remains an orphan receptor whose ligands and functions are poorly understood. In the present study, we sought to evaluate the level of TLR10 expression in breastmilk (BM) and explore its potential function in the context of HIV-1 infection. We evaluated HIV-1-infected (Nigerian: n = 40) and uninfected (Nigerian: n = 27; Canadian: n = 15) BM samples for TLR expression (i.e., TLR10, TLR2, and TLR1) and report here that HIV-1-infected BM from Nigerian women showed significantly higher levels of TLR10, TLR1, and TLR2 expression. Moreover, the level of TLR10 expression in HIV-1-infected BM was upregulated by over 100-fold compared to that from uninfected control women. In vitro studies using TZMbl cells demonstrated that TLR10 overexpression contributes to higher HIV-1 infection and proviral DNA integration. Conversely, TLR10 inhibition significantly decreased HIV-1 infection. Notably, HIV-1 gp41 was recognized as a TLR10 ligand, leading to the induction of IL-8 and NF-kBa activation. The identification of a TLR10 ligand and its involvement in HIV-1 infection enhances our current understanding of HIV-1 replication and may assist in the development of improved future therapeutic strategies

Expression profiling of human milk derived exosomal microRNAs and their targets in HIV‐1 infected mothers

Despite the use of antiretroviral therapy (ART) in HIV‐1 infected mothers approximately 5% of new HIV‐1 infections still occur in breastfed infants annually, which warrants for the development of novel strategies to prevent new HIV‐1 infections in infants. Human milk (HM) exosomes are highly enriched in microRNAs (miRNAs), which play an important role in neonatal immunity. Furthermore, HM exosomes from healthy donors are known to inhibit HIV‐1 infection and transmission; however, the effect of HIV‐1 on HM exosomal miRNA signatures remains unknown. In this study, we used nCounter NanoString technology and investigated miRNAs expression profiles in first week postpartum HM exosomes from HIV‐1 infected and uninfected control mothers (n = 36). Our results indicated that HIV‐1 perturbed the differential expression patterns of 19 miRNAs (13 upregulated and 6 downregulated) in HIV‐1 infected women compared to healthy controls. DIANA‐miR functional pathway analyses revealed that multiple biological pathways are involved including cell cycle, pathways in cancer, TGF‐β signaling, FoxO signaling, fatty acid biosynthesis, p53 signaling and apoptosis. Moreover, the receiver operating characteristics (ROC) curve analyses of miR‐630 and miR‐ 378g yielded areas under the ROC curves of 0.82 (95% CI 0.67 to 0.82) and 0.83 (95% CI 0.67 to 0.83), respectively highlighting their potential to serve as biomarkers to identify HIV‐1 infection in women. These data may contribute to the development of new therapeutic strategies in prevention of mother‐ to‐child transmission (MTCT) of HIV‐1

Expression profiling of human milk derived exosomal microRNAs and their targets in HIV-1 infected mothers

Abstract Despite the use of antiretroviral therapy (ART) in HIV-1 infected mothers approximately 5% of new HIV-1 infections still occur in breastfed infants annually, which warrants for the development of novel strategies to prevent new HIV-1 infections in infants. Human milk (HM) exosomes are highly enriched in microRNAs (miRNAs), which play an important role in neonatal immunity. Furthermore, HM exosomes from healthy donors are known to inhibit HIV-1 infection and transmission; however, the effect of HIV-1 on HM exosomal miRNA signatures remains unknown. In this study, we used nCounter NanoString technology and investigated miRNAs expression profiles in first week postpartum HM exosomes from HIV-1 infected and uninfected control mothers (n = 36). Our results indicated that HIV-1 perturbed the differential expression patterns of 19 miRNAs (13 upregulated and 6 downregulated) in HIV-1 infected women compared to healthy controls. DIANA-miR functional pathway analyses revealed that multiple biological pathways are involved including cell cycle, pathways in cancer, TGF-β signaling, FoxO signaling, fatty acid biosynthesis, p53 signaling and apoptosis. Moreover, the receiver operating characteristics (ROC) curve analyses of miR-630 and miR-378g yielded areas under the ROC curves of 0.82 (95% CI 0.67 to 0.82) and 0.83 (95% CI 0.67 to 0.83), respectively highlighting their potential to serve as biomarkers to identify HIV-1 infection in women. These data may contribute to the development of new therapeutic strategies in prevention of mother-to-child transmission (MTCT) of HIV-1

Comprehensive reference ranges for hematology and clinical chemistry laboratory parameters derived from normal Nigerian adults.

Interpretation of laboratory test results with appropriate diagnostic accuracy requires reference or cutoff values. This study is a comprehensive determination of reference values for hematology and clinical chemistry in apparently healthy voluntary non-remunerated blood donors and pregnant women.Consented clients were clinically screened and counseled before testing for HIV, Hepatitis B, Hepatitis C and Syphilis. Standard national blood donors' questionnaire was administered to consented blood donors. Blood from qualified volunteers was used for measurement of complete hematology and chemistry parameters. Blood samples were analyzed from a total of 383 participants, 124 (32.4%) males, 125 (32.6%) non-pregnant females and 134 pregnant females (35.2%) with a mean age of 31 years. Our results showed that the red blood cells count (RBC), Hemoglobin (HB) and Hematocrit (HCT) had significant gender difference (p = 0.000) but not for total white blood count (p>0.05) which was only significantly higher in pregnant verses non-pregnant women (p = 0.000). Hemoglobin and Hematocrit values were lower in pregnancy (P = 0.000). Platelets were significantly higher in females than men (p = 0.001) but lower in pregnant women (p =  .001) with marked difference in gestational period. For clinical chemistry parameters, there was no significant difference for sodium, potassium and chloride (p>0.05) but gender difference exists for Bicarbonate (HCO3), Urea nitrogen, Creatinine as well as the lipids (p<0.05). Total bilirubin was significantly higher in males than females (p = 0.000). Significant differences exist for all chemistry parameters between pregnant and non-pregnant women in this study (p<0.05), except Amylase and total cholesterol (p>0.05).Hematological and Clinical Chemistry reference ranges established in this study showed significant gender differences. Pregnant women also differed from non-pregnant females and during pregnancy. This is the first of such comprehensive study to establish reference values among adult Nigerians and difference observed underscore the need to establish reference values for different populations

Implementing quality assurance for laboratory-based and point-of-care HIV testing in Nigeria

No abstract available

CD4 absolute Count for normal adults and pregnant women in Nigeria.

<p>P-value 0.001.</p

Clinical chemistry parameters for pregnant women at different trimesters in Nigeria.

<p>Clinical chemistry parameters for pregnant women at different trimesters in Nigeria.</p

Hematological parameters at different trimester for pregnant women in Nigeria.

<p>Hematological parameters at different trimester for pregnant women in Nigeria.</p