Abstract
CCR5: A receptor at the center stage in infection CCR5: As receptor that has shaped scienceThe human C-C chemokine receptor type 5 (CCR5) is mostly expressed on the surface of leukocytes, playing a pivotal role in inflammatory responses and other immune functions (Figure 1) (1, 2).In 1996, CCR5 was reported as the HIV-1 co-receptor (3), and the 32-nucleotide deletion in the CCR5 gene (CCR5D32) was reported as a resistance factor to HIV-1 infection (4, 5).These discoveries massively advanced HIV-1 research, bringing insights into resistance mechanisms against HIV-1 and leading to the development of new anti-viral therapies.The clinical use of the CCR5 antagonist maraviroc for HIV-1 treatment was approved in 2007, and cases of sustained remission of HIV-1 infection following stem-cell transplantation using CCR5D32 homozygous cells were reported in the following years (e.g., the Berlin Patient in 2009 and the London Patient in 2019) (2, 6, 7).CCR5 was initially studied in different populations in the context of HIV-1 infection.More recently, it has become clear that CCR5 influences various health and pathological conditions, including infectious diseases other than HIV-1 infection.For example, CCR5 and its agonists participate in the immune responses to Zika virus (8), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (9), Schistosoma spp.(10), among other pathogens (2, 10), and the CCR5 D32 variant is a critical risk factor for symptomatic West Nile virus infection (11,12).Moreover, human pathogens, such as Toxoplasma gondii produce CCR5-binding molecules that can affect immune response to infection as well as block R5 tropic HIV-1 entry in CCR5-expressing cells (13-15).Therapies involving CCR5 blockade have advanced substantially, with the potential to be applied in infectious and non-infectious diseases (1, 16, 17).CCR5 also drives several debates, including those on gene-editing technologies (18) and chemokine system Frontiers in Immunology frontiersin.