Lipophagy Confers a Key Metabolic Advantage That Ensures Protective CD8A T-Cell Responses against HIV-1

Scientists showed that, after both polyclonal and HIV-1-specific activation, CD8A T-cells from ART displayed reduced autophagy-dependent degradation of lysosomal contents when compared to naturally HIV-1 protected elite controllers.
[Autophagy]
Loucif, H., Dagenais-Lussier, X., Beji, C., Cassin, L., Jrade, H., Tellitchenko, R., Routy, J.-P., Olagnier, D., & Grevenynghe, J. van. (2021). Lipophagy confers a key metabolic advantage that ensures protective CD8A T-cell responses against HIV-1. Autophagy, 0(0), 1–16. https://doi.org/10.1080/15548627.2021.1874134 Cite
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Generation of HIV-Resistant Cells with a Single-Domain Antibody: Implications for HIV-1 Gene Therapy

GPI-anchored m36.4, a single-domain antibody targeting the coreceptor-binding site of gp120, was constructed with a lentiviral vector. Scientists verified that m36.4 was efficiently expressed on the plasma membrane of transduced TZM-bl cells and targeted lipid raft sites without affecting the expression of HIV receptors
[Cellular & Molecular Immunology]
Jin, H., Tang, X., Li, L., Chen, Y., Zhu, Y., Chong, H., & He, Y. (2021). Generation of HIV-resistant cells with a single-domain antibody: implications for HIV-1 gene therapy. Cellular & Molecular Immunology, 1–15. https://doi.org/10.1038/s41423-020-00627-y Cite
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Heightened Resistance To Host Type 1 Interferons Characterizes HIV-1 at Transmission and After Antiretroviral Therapy Interruption

Researchers characterized the IFN-I sensitivity of 500 clonally derived HIV-1 isolates from the plasma and CD4+ T cells of 26 individuals sampled longitudinally after transmission or after antiretroviral therapy and analytical treatment interruption.
[Science Translational Medicine]
Gondim, M. V. P., Sherrill-Mix, S., Bibollet-Ruche, F., Russell, R. M., Trimboli, S., Smith, A. G., Li, Y., Liu, W., Avitto, A. N., DeVoto, J. C., Connell, J., Fenton-May, A. E., Pellegrino, P., Williams, I., Papasavvas, E., Lorenzi, J. C. C., Salantes, D. B., Mampe, F., Monroy, M. A., … Hahn, B. H. (2021). Heightened resistance to host type 1 interferons characterizes HIV-1 at transmission and after antiretroviral therapy interruption. Science Translational Medicine, 13(576). https://doi.org/10.1126/scitranslmed.abd8179 Cite
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Vaccination Induces Maturation in a Mouse Model of Diverse Unmutated VRC01-Class Precursors to HIV-Neutralizing Antibodies With >50% Breadth

Using sequential immunization of immunoglobulin-humanized mice expressing diverse unmutated VRC01-class antibody precursors, scientists elicited serum responses capable of neutralizing viruses bearing glycan276 and isolated multiple lineages of VRC01-class bnAbs, including two with >50% breadth on a 208-strain panel.
[Immunity]
Chen, X., Zhou, T., Schmidt, S. D., Duan, H., Cheng, C., Chuang, G.-Y., Gu, Y., Louder, M. K., Lin, B. C., Shen, C.-H., Sheng, Z., Zheng, M. X., Doria-Rose, N. A., Joyce, M. G., Shapiro, L., Tian, M., Alt, F. W., Kwong, P. D., & Mascola, J. R. (2021). Vaccination induces maturation in a mouse model of diverse unmutated VRC01-class precursors to HIV-neutralizing antibodies with >50% breadth. Immunity, 0(0). https://doi.org/10.1016/j.immuni.2020.12.014 Cite
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The HIV Protease Inhibitor Saquinavir Attenuates Sepsis-Induced Acute Lung Injury and Promotes M2 Macrophage Polarization via Targeting Matrix Metalloproteinase-9

Scientists focused on the important role of macrophage polarization in cecal ligation puncture-mediated acute lung injury and determined the ability of saquinavir to maintain M2 over M1 phenotype partially through the inhibition of matrix metalloproteinase-9.
[Cell Death & Disease]
Tong, Y., Yu, Z., Chen, Z., Zhang, R., Ding, X., Yang, X., Niu, X., Li, M., Zhang, L., Billiar, T. R., Pitt, B. R., & Li, Q. (2021). The HIV protease inhibitor Saquinavir attenuates sepsis-induced acute lung injury and promotes M2 macrophage polarization via targeting matrix metalloproteinase-9. Cell Death & Disease, 12(1), 1–14. https://doi.org/10.1038/s41419-020-03320-0 Cite
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Recapitulation of HIV-1 Env-Antibody Coevolution in Macaques Leading to Neutralization Breadth

Neutralizing antibodies elicited by HIV-1 in naturally infected humans coevolve with viral envelope proteins in distinctive molecular patterns, in some cases acquiring substantial breadth.
[Science]
Roark, R. S., Li, H., Williams, W. B., Chug, H., Mason, R. D., Gorman, J., Wang, S., Lee, F.-H., Rando, J., Bonsignori, M., Hwang, K.-K., Saunders, K. O., Wiehe, K., Moody, M. A., Hraber, P. T., Wagh, K., Giorgi, E. E., Russell, R. M., Bibollet-Ruche, F., … Shaw, G. M. (2021). Recapitulation of HIV-1 Env-antibody coevolution in macaques leading to neutralization breadth. Science, 371(6525). https://doi.org/10.1126/science.abd2638 Cite
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CRISPR Therapeutics Receives Grant to Advance In Vivo CRISPR/Cas9 Gene Editing Therapies for HIV

CRISPR Therapeutics AG announced the receipt of a grant from the Bill & Melinda Gates Foundation to research in vivo gene editing therapies for the treatment of HIV.
[CRISPR Therapeutics AG]
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HIV Antibody Fc N-Linked Glycosylation Is Associated with Viral Rebound

Using a comprehensive antibody Fc-profiling approach, the level of HIV-specific antibody Fc N-galactosylation was significantly associated with time to rebound after treatment discontinuation across three independent cohorts.
[Cell Reports]
Offersen, R., Yu, W.-H., Scully, E. P., Julg, B., Euler, Z., Sadanand, S., Garcia-Dominguez, D., Zheng, L., Rasmussen, T. A., Jennewein, M. F., Linde, C., Sassic, J., Lofano, G., Vigano, S., Stephenson, K. E., Fischinger, S., Suscovich, T. J., Lichterfeld, M., Lauffenburger, D., … Alter, G. (2020). HIV Antibody Fc N-Linked Glycosylation Is Associated with Viral Rebound. Cell Reports, 33(11). https://doi.org/10.1016/j.celrep.2020.108502 Cite
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HIV Skews a Balanced Mtb-Specific Th17 Response in Latent Tuberculosis Subjects to a Pro-inflammatory Profile Independent of Viral Load

Scientists determined whether HIV infection of latent tuberculosis-infected subjects compromised the balanced Mycobacterium tuberculosis-specific T helper 17 response of recognized importance in anti-TB immunity.
[Cell Reports]
Rakshit, S., Hingankar, N., Alampalli, S. V., Adiga, V., Sundararaj, B. K., Sahoo, P. N., Finak, G., J, A. J. U. K., Dhar, C., D’Souza, G., Virkar, R. G., Ghate, M., Thakar, M. R., Paranjape, R. S., Rosa, S. C. D., Ottenhoff, T. H. M., & Vyakarnam, A. (2020). HIV Skews a Balanced Mtb-Specific Th17 Response in Latent Tuberculosis Subjects to a Pro-inflammatory Profile Independent of Viral Load. Cell Reports, 33(9). https://doi.org/10.1016/j.celrep.2020.108451 Cite
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Multiplexed CRISPR/CAS9-Mediated Engineering of Pre-Clinical Mouse Models Bearing Native Human B Cell Receptors

Scientists report a oneā€step CRISPR/Cas9 KI methodology to combine the insertion of human germline immunoglobulin heavy and light chains at their endogenous loci in mice.
[EMBO Journal]
Wang, X., Ray, R., Kratochvil, S., Melzi, E., Lin, Y.-C., Giguere, S., Xu, L., Warner, J., Cheon, D., Liguori, A., Groschel, B., Phelps, N., Adachi, Y., Tingle, R., Wu, L., Crotty, S., Kirsch, K. H., Nair, U., Schief, W. R., & Batista, F. D. (2020). Multiplexed CRISPR/CAS9-mediated engineering of pre-clinical mouse models bearing native human B cell receptors. The EMBO Journal, n/a(n/a), e105926. https://doi.org/10.15252/embj.2020105926 Cite
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Food Insecurity and T-Cell Dysregulation in Women Living with HIV on Antiretroviral Therapy

Food insecurity was associated with increased activation of CD4+ and CD8+ T-cells, increased senescence of CD8+ T-cells, and decreased co-stimulation of CD4+ and CD8+ T-cells
[Clinical Infectious Diseases]
Peters, B. A., Sheira, L. A., Hanna, D. B., Qi, Q., Sharma, A., Adedimeji, A., Wilson, T., Merenstein, D., Tien, P. C., Cohen, M., Wentz, E. L., Kinslow, J., Landay, A. L., & Weiser, S. D. (n.d.). Food insecurity and T-cell dysregulation in women living with HIV on antiretroviral therapy. Clinical Infectious Diseases. https://doi.org/10.1093/cid/ciaa1771 Cite
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