Virus Entry via the Alternative Coreceptors CCR3 and FPRL1 Differs by Human Immunodeficiency Virus Type 1 Subtype

Nedellec, Rebecca; Coetzer, Mia; Shimizu, Nobuaki; Hoshino, Hiroo; Polonis, Victoria R.; Morris, Lynn; Mårtensson, Ulrika; Binley, James Μ.; Overbaugh, Julie; Mosier, Donald E.

doi:10.1128/jvi.00780-09

Cited by 39 publications

(55 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, SIVsmm from sooty mangabeys can also use a coreceptor other than CCR5 to mediate infection in vivo: genetic absence of CCR5 is relatively common in sooty mangabeys, but CCR5-negative animals are still infected with SIVsmm, though their virus loads are, on average, one-half log less than what is typically seen in CCR5 ϩ animals (49). The coreceptor used by SIVsmm to replicate in sooty mangabeys has not yet been identified, though in vitro and genetic studies appear to rule (3,4,10,23,47,66), with CCR3, GPR15, APJ, and FPRL-1 being among those most frequently used (11,26,43,47,57). However, these studies have typically employed cell lines that likely overexpress these coreceptors, so it is difficult to assess whether utilization of these coreceptors can lead to infection of primary human cell types.…”

Section: Discussionmentioning

confidence: 99%

“…The supernatant was collected daily, and virus replication was monitored by measuring the p24 antigen content using the Alliance HIV-1 p24 Antigen ELISA kit (PerkinElmer, Boston, MA). Coreceptor usage was also determined on NP-2 cells expressing CD4 along with either CCR5, CXCR4, or other G protein-coupled receptors with Env pseudovirions as previously described (43,57).…”

Section: Methodsmentioning

confidence: 99%

“…Although some HIV-1 strains are able to use a variety of different G protein-coupled receptors to gain entry into CD4 ϩ cell lines, the great majority of these viruses use CCR5 and/or CXCR4 as coreceptors to infect primary cells (3,4,10,23,47,66). CCR3, GPR15, APJ, and FPRL-1 are among the most frequently used alternative coreceptors when overexpressed on cell lines (11,26,43,47,57). Rare cases of HIV-1 strains that are able to use FPRL-1 and GPR1, but not CCR5 or CXCR4, have been reported (57); however, their in vivo relevance remains unknown.…”

Section: The Molecularly Cloned (Single) T/f Virus Was Able To Replicmentioning

confidence: 99%

See 2 more Smart Citations

Primary Infection by a Human Immunodeficiency Virus with Atypical Coreceptor Tropism

Jiang

Parrish

Wilen

et al. 2011

J Virol

View full text Add to dashboard Cite

The great majority of human immunodeficiency virus type 1 (HIV-1) strains enter CD4؉ target cells by interacting with one of two coreceptors, CCR5 or CXCR4. Here we describe a transmitted/founder (T/F) virus (ZP6248) that was profoundly impaired in its ability to utilize CCR5 and CXCR4 coreceptors on multiple CD4؉ cell lines as well as primary human CD4 ؉ T cells and macrophages in vitro yet replicated to very high titers (>80 million RNA copies/ml) in an acutely infected individual. Interestingly, the envelope (Env) glycoprotein of this clade B virus had a rare GPEK sequence in the crown of its third variable loop (V3) rather than the consensus GPGR sequence. Extensive sequencing of sequential plasma samples showed that the GPEK sequence was present in virtually all Envs, including those from the earliest time points after infection. The molecularly cloned (single) T/F virus was able to replicate, albeit poorly, in cells obtained from ccr5⌬32 homozygous donors. The ZP6248 T/F virus could also infect cell lines overexpressing the alternative coreceptors GPR15, APJ, and FPRL-1. A single mutation in the V3 crown sequence (GPEK->GPGK) of ZP6248 restored its infectivity in CCR5؉ cells but reduced its ability to replicate in GPR15 ؉ cells, indicating that the V3 crown motif played an important role in usage of this alternative coreceptor. These results suggest that the ZP6248 T/F virus established an acute in vivo infection by using coreceptor(s) other than CCR5 or CXCR4 or that the CCR5 coreceptor existed in an unusual conformation in this individual.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: The Molecularly Cloned (Single) T/f Virus Was Able To Replicmentioning

confidence: 99%

See 1 more Smart Citation

Primary Infection by a Human Immunodeficiency Virus with Atypical Coreceptor Tropism

Jiang

Parrish

Wilen

et al. 2011

J Virol

View full text Add to dashboard Cite

show abstract

“…Early studies performed by Nedellec et al [2] established that NP-2/CD4/CCR6 constructed cells permitted a low entry of HIV-1 pseudotyped with two simian immunodeficiency virus (SIV) envelope glycoproteins, gp160 and gp140, compared with other chemokine co-receptor constructs. Conversely, HIV envelope-pseudotyped viruses (subtypes A-D) taken from 15 patients did not permit entry via CCR6 above background.…”

Section: Ccr6 As An Hiv Co-receptormentioning

confidence: 99%

“…Recent times, however, have focused on the virus' uses of an expanded repertoire of chemokine receptors for this purpose [1,2]. One such receptor is CCR6 -a seven-transmembrane domain G-protein-coupled receptor whose gene is found on chromosome 6q27 [3].…”

Section: Ccr6/ccl20 Axis Biologymentioning

confidence: 99%

CCR6/CCL20 chemokine axis in human immunodeficiency virus immunity and pathogenesis

Lee

Körner

2017

Journal of General Virology

View full text Add to dashboard Cite

Recent studies in human immunodeficiency virus (HIV) have garnered interest for the role of CC chemokine receptor 6 (CCR6) and its known ligands, CC chemokine ligand 20 (CCL20) and human b-defensins, in viral entry, dissemination and antiviral immunity. Several studies have suggested that CCR6 may also act as a weak co-receptor of HIV entry, in addition to the canonical CXC chemokine receptor 4 (CXCR4) and CCR5. However, the pathogenic significance has yet to be demonstrated as the observations for preferential infection of CD4 + CCR6 + over CD4 + CCR6 À T cells appear to be independent of CCR6 expression. This indicates means for preferential infection other than CCR6 co-receptor use. Attention has also turned to the inadvertent role of the CCR6/CCL20 axis in attracting key immune cells, including T H 17 cells and dendritic cells, to sites of infection and propagating the virus to other sites of the body. This review article will summarize the latest evidence that the CCR6/CCL20 chemokine axis is playing an important role in HIV pathogenesis and immunity. Further work with in vivo studies is needed to establish the biological and, hence, therapeutic significance of these findings.

show abstract

Inflammatory Mechanisms and Cascades Contributing to Neurocognitive Impairment in HIV/AIDS

Fernandes

Pulliam

2019

Neurocognitive Complications of HIV-Infection

View full text Add to dashboard Cite

Virus Entry via the Alternative Coreceptors CCR3 and FPRL1 Differs by Human Immunodeficiency Virus Type 1 Subtype

Abstract: Human immunodeficiency virus type 1 (HIV-1) infects target cells by binding to

Cited by 39 publications

References 81 publications

Primary Infection by a Human Immunodeficiency Virus with Atypical Coreceptor Tropism

Primary Infection by a Human Immunodeficiency Virus with Atypical Coreceptor Tropism

CCR6/CCL20 chemokine axis in human immunodeficiency virus immunity and pathogenesis

Inflammatory Mechanisms and Cascades Contributing to Neurocognitive Impairment in HIV/AIDS

Contact Info

Product

Resources

About