Disruption of CCR5 expression by lentiviral vector-mediated CRISPR/SaCas9 led to increased resistance against HIV-1 infection in human primary CD4<sup>+</sup> T cells.
Recently, a second individual (the "London patient") with HIV-1 infection and concomitant leukemia was cured of both diseases by a conditioning myeloablative regimen followed by transplantation of stem cells bearing the homozygous CCR5 Δ32 mutation.
A London patient living with HIV-1 has become the second person to achieve remission from HIV-1 infection for >1 year after receiving a bone marrow stem cell transplant from a donor with cells resistant to CCR5-tropic HIV-1 infection (Gupta et al.Nature 2019;568:244-248).
Furthermore, we determined that SLAMF7 activation on monocytes is able to decrease their susceptibility to HIV-1 infection in vitro via downregulation of CCR5 and upregulation of the CCL3L1 chemokine.
C-C chemokine receptor 5 (CCR5) has attracted wide concern for its critical role in the progression of human immunodeficiency virus type 1 (HIV-1) infection.
Moreover, while both Mϕ subsets express comparable surface protein levels of the HIV-1 receptor and co-receptor, CD4 and CCR5 respectively, the IL-34-Mϕs express significantly greater levels of pertinent restriction factor genes, potentially accounting for their greater resistance to HIV-1 infection than that observed in M-CSF-Mϕs.
Previous research has proven that disruption of either the CCR5 or the CXCR4 gene confers resistance to R5-tropic or X4-tropic human immunodeficiency virus type 1 (HIV-1) infection, respectively.
When plasma viremia reached >10<sup>7</sup> copies/mL 3 weeks after HIV-1 infection, the mice were myeloablated with busulfan and transplanted with anti-HIV-1 gene-modified CD34<sup>+</sup> HSPCs transduced with a lentiviral vector expressing two short hairpin RNAs (shRNAs) against CCR5 and HIV-1 long terminal repeat (LTR), along with human thymus tissue under the kidney capsule.
The pooled odds ratio (ORs) along with its 95% credible interval (95%CI) was used to evaluate the relation between the CCR5-delta32 polymorphism and HIV-1 infection risk.
The article also throws light on the SAR studies and most prevalent mutations in the receptor for designing CCR5 antagonists that can combat HIV-1 infection.
Sequence analysis of target cell line GHOST-CCR5-CXCR4 and human primary CD4 T cells showed that the double-strand breaks at the TALEN targeted sites resulted in truncated or nonfunctional CCR5 proteins thereby conferring protection against HIV-1 infection in vitro.
To develop a novel supplemental or alternative therapeutic for CCR5-tropic (R5) HIV-1 infection, we generated a recombinant vesicular stomatitis virus (rVSV) in which the gene encoding its envelope glycoprotein (G) was replaced with the genes encoding R5 HIV-1 receptors (human CD4 and CCR5), designated VSVΔG-CC5.
These data demonstrate that TFR cells are highly permissive to R5-tropic HIV-1 both <i>ex vivo</i> and <i>in vivo</i> This is likely related to elevated CCR5 levels combined with a heightened proliferative state and suggests that TFR cells contribute to persistent R5-tropic HIV-1 replication <i>in vivo</i><b>IMPORTANCE</b> In chronic, untreated HIV-1 infection, viral replication is concentrated in secondary lymphoid follicles.
Because CCR5-negative T cells are resistant to HIV-1 infection, CCR5-negative anti-CD19 chimeric antigen receptor (CAR) T cells could be used to treat patients with HIV-associated B cell malignancies.