A formylpeptide receptor, FPRL1, acts as an efficient coreceptor for primary isolates of human immunodeficiency virus

<p>Abstract</p> <p>Background</p> <p>More than 10 members of seven-transmembrane G protein-coupled receptors (GPCRs) have been shown to work as coreceptors for human immunodeficiency virus type 1 (HIV-1), HIV type 2 (HIV-2), and simian immunodeficiency viruses (SIVs). As a common feature of HIV/SIV coreceptors, tyrosine residues are present with asparagines, aspartic acids or glutamic acids in the amino-terminal extracellular regions (NTRs).</p> <p>We noticed that a receptor for N-formylpeptides, FPRL1, also contains two tyrosine residues accompanied by glutamic acids in its NTR. It was reported that monocytes expressing CCR5 and FPRL1 in addition to CD4 are activated by treatment with ligands or agonists of FPRL1. Activated monocytes down-modulate CCR5 and become resistant to infection by HIV-1 strains. Thus, FPRL1 plays important roles in protection of monocyptes against HIV-1 infection. However, its own coreceptor activity has not been elucidated yet. In this study, we examined coreceptor activities of FPRL1 for HIV/SIV strains including primary HIV-1 isolates.</p> <p>Results</p> <p>A CD4-transduced human glioma cell line, NP-2/CD4, is strictly resistant to HIV/SIV infection. We have reported that when NP-2/CD4 cells are transduced with a GPCR having coreceptor activity, the cells become susceptible to HIV/SIV strains. When NP-2/CD4 cells were transduced with FPRL1, the resultant NP-2/CD4/FPRL1 cells became markedly susceptible to some laboratory-adapted HIV/SIV strains. We found that FPRL1 is also efficiently used as a coreceptor by primary HIV-1 isolates as well as CCR5 or CXCR4.</p> <p>Amino acid sequences linked to the FPRL1 use could not be detected in the V3 loop of the HIV-1 Env protein. Coreceptor activities of FPRL1 were partially blocked by the forymyl-Met-Leu-Phe (fMLF) peptide.</p> <p>Conclusion</p> <p>We conclude that FPRL1 is a novel and efficient coreceptor for HIV/SIV strains. FPRL1 works as a bifunctional factor in HIV-1 infection. Namely, the role of FPRL1 in HIV-1 infection is protective and/or promotive in different conditions. FPRL1 has been reported to be abundantly expressed in the lung, spleen, testis, and neutrophils. We detected mRNA expression of FPRL1 in 293T (embryonal kidney cell line), C8166 (T cell line), HOS (osteosarcoma cell line), Molt4#8 (T cell line), U251MG (astrocytoma cell line), U87/CD4 (CD4-transduced glioma cell line), and peripheral blood lymphocytes. Roles of FPRL1 in HIV-1 infection <it>in vivo </it>should be further investigated.</p

A formylpeptide receptor, FPRL1, acts as an efficient coreceptor for primary isolates of human immunodeficiency virus-6

the fMLF peptide (B) or RANTES for two hours at 37°C (C), and then inoculated with two HIV-1 strains, GUN-7WT (○ and ●) and HCM342 (□ and ■), HIV-2 CBL23 strain (△ and ▲), and SIV mndGB-1 strain (◇ and ◆). Six days after infection, cells positive for HIV-1 antigens were detected by IFA using a fluorescence microscope.<p><b>Copyright information:</b></p><p>Taken from "A formylpeptide receptor, FPRL1, acts as an efficient coreceptor for primary isolates of human immunodeficiency virus"</p><p>http://www.retrovirology.com/content/5/1/52</p><p>Retrovirology 2008;5():52-52.</p><p>Published online 25 Jun 2008</p><p>PMCID:PMC2453146.</p><p></p

A formylpeptide receptor, FPRL1, acts as an efficient coreceptor for primary isolates of human immunodeficiency virus-4

after infection, cells positive for HIV-1 antigens were detected by IFA using a fluorescence microscope. Percentage of cells judged to be positive for IFA are shown.<p><b>Copyright information:</b></p><p>Taken from "A formylpeptide receptor, FPRL1, acts as an efficient coreceptor for primary isolates of human immunodeficiency virus"</p><p>http://www.retrovirology.com/content/5/1/52</p><p>Retrovirology 2008;5():52-52.</p><p>Published online 25 Jun 2008</p><p>PMCID:PMC2453146.</p><p></p

A formylpeptide receptor, FPRL1, acts as an efficient coreceptor for primary isolates of human immunodeficiency virus-3

S were completely resistant to all these HIV-1 isolates (E). The origins and subtypes of these primary isolates are summarized (see Additional file ).<p><b>Copyright information:</b></p><p>Taken from "A formylpeptide receptor, FPRL1, acts as an efficient coreceptor for primary isolates of human immunodeficiency virus"</p><p>http://www.retrovirology.com/content/5/1/52</p><p>Retrovirology 2008;5():52-52.</p><p>Published online 25 Jun 2008</p><p>PMCID:PMC2453146.</p><p></p

A formylpeptide receptor, FPRL1, acts as an efficient coreceptor for primary isolates of human immunodeficiency virus-7

the methods described in the DDBJ website (National Institute of Genetics, Center for Information Biology and DNA Databank of Japan, ). FPRL1 is indicated by the arrow. GPCRs reported to function as HIV/SIV coreceptors are indicated by "*".<p><b>Copyright information:</b></p><p>Taken from "A formylpeptide receptor, FPRL1, acts as an efficient coreceptor for primary isolates of human immunodeficiency virus"</p><p>http://www.retrovirology.com/content/5/1/52</p><p>Retrovirology 2008;5():52-52.</p><p>Published online 25 Jun 2008</p><p>PMCID:PMC2453146.</p><p></p

A formylpeptide receptor, FPRL1, acts as an efficient coreceptor for primary isolates of human immunodeficiency virus-5

Oculation. NP-2/CD4 cells were completely resistant to these HIV-2 strains (E). These results are summarized (see Additional file ).<p><b>Copyright information:</b></p><p>Taken from "A formylpeptide receptor, FPRL1, acts as an efficient coreceptor for primary isolates of human immunodeficiency virus"</p><p>http://www.retrovirology.com/content/5/1/52</p><p>Retrovirology 2008;5():52-52.</p><p>Published online 25 Jun 2008</p><p>PMCID:PMC2453146.</p><p></p

A formylpeptide receptor, FPRL1, acts as an efficient coreceptor for primary isolates of human immunodeficiency virus-0

the methods described in the DDBJ website (National Institute of Genetics, Center for Information Biology and DNA Databank of Japan, ). FPRL1 is indicated by the arrow. GPCRs reported to function as HIV/SIV coreceptors are indicated by "*".<p><b>Copyright information:</b></p><p>Taken from "A formylpeptide receptor, FPRL1, acts as an efficient coreceptor for primary isolates of human immunodeficiency virus"</p><p>http://www.retrovirology.com/content/5/1/52</p><p>Retrovirology 2008;5():52-52.</p><p>Published online 25 Jun 2008</p><p>PMCID:PMC2453146.</p><p></p

A formylpeptide receptor, FPRL1, acts as an efficient coreceptor for primary isolates of human immunodeficiency virus-1

T-PCR was done using serially diluted (1:1, 1:10, 1:100, 1:1000, and 1:10000) cDNA reverse-transcribed from the total RNA. As a control, the expression level of GAPDH mRNA in each cDNA preparation was determined by RT-PCR. (B) mRNA expression for four GPCRs in 11 kinds of human cells as detected by RT-PCR using the specific primers. As a control, the expression level of GAPDH mRNA in each cDNA preparation was determined by RT-PCR. The PCR primers amplify 1,377 (CD4), 1,059 (CCR5 and CXCR4), 1,056 (FPRL1), 1,068 (GPR1), and 1,008 (GAPDH) base-pair DNA fragments when these genes are expressed in the cells. Expression level, (-~++) were determined by intensities of amplified DNA bands compared to those of the corresponding controls (GAPDH).<p><b>Copyright information:</b></p><p>Taken from "A formylpeptide receptor, FPRL1, acts as an efficient coreceptor for primary isolates of human immunodeficiency virus"</p><p>http://www.retrovirology.com/content/5/1/52</p><p>Retrovirology 2008;5():52-52.</p><p>Published online 25 Jun 2008</p><p>PMCID:PMC2453146.</p><p></p