P-selectin glycoprotein ligand-1 (PSGL-1/CD162) is incorporated into clinical HIV-1 isolates and can mediate virus capture and subsequent transfer to permissive ... View Full Text


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Article Info

DATE

2022-05-21

AUTHORS

Jonathan Burnie, Arvin Tejnarine Persaud, Laxshaginee Thaya, Qingbo Liu, Huiyi Miao, Stephen Grabinsky, Vanessa Norouzi, Paolo Lusso, Vera A. Tang, Christina Guzzo

ABSTRACT

BackgroundP-selectin glycoprotein ligand-1 (PSGL-1/CD162) has been studied extensively for its role in mediating leukocyte rolling through interactions with its cognate receptor, P-selectin. Recently, PSGL-1 was identified as a novel HIV-1 host restriction factor, particularly when expressed at high levels in the HIV envelope. Importantly, while the potent antiviral activity of PSGL-1 has been clearly demonstrated in various complementary model systems, the breadth of PSGL-1 incorporation across genetically diverse viral isolates and clinical isolates has yet to be described. Additionally, the biological activity of virion-incorporated PSGL-1 has also yet to be shown.ResultsHerein we assessed the levels of PSGL-1 on viruses produced through transfection with various amounts of PSGL-1 plasmid DNA (0–250 ng), compared to levels of PSGL-1 on viruses produced through infection of T cell lines and primary PBMC. We found that very low levels of PSGL-1 plasmid DNA (< 2.5 ng/well) were necessary to generate virus models that could closely mirror the phenotype of viruses produced via infection of T cells and PBMC. Unique to this study, we show that PSGL-1 is incorporated in a broad range of HIV-1 and SIV isolates and that virions with incorporated PSGL-1 are detectable in plasma from viremic HIV-1-infected individuals, corroborating the relevance of PSGL-1 in natural infection. Additionally, we show that PSGL-1 on viruses can bind its cognate selectin receptors, P-, E-, and L-selectins. Finally, we show viruses with endogenous levels of PSGL-1 can be captured by P-selectin and transferred to HIV-permissive bystander cells, highlighting a novel role for PSGL-1 in HIV-1 infection. Notably, viruses which contained high levels of PSGL-1 were noninfectious in our hands, in line with previous findings reporting the potent antiviral activity of PSGL-1.ConclusionsOur results indicate that levels of PSGL-1 incorporation into virions can vary widely among model systems tested, and that careful tailoring of plasmid levels is required to recapitulate physiological systems when using pseudovirus models. Taken together, our data suggest that PSGL-1 may play diverse roles in the physiology of HIV-1 infection, particularly due to the functionally active state of PSGL-1 on virion surfaces and the breadth of PSGL-1 incorporation among a wide range of viral isolates. More... »

PAGES

9

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12977-022-00593-5

DOI

http://dx.doi.org/10.1186/s12977-022-00593-5

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1148062669

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/35597982


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26 schema:description BackgroundP-selectin glycoprotein ligand-1 (PSGL-1/CD162) has been studied extensively for its role in mediating leukocyte rolling through interactions with its cognate receptor, P-selectin. Recently, PSGL-1 was identified as a novel HIV-1 host restriction factor, particularly when expressed at high levels in the HIV envelope. Importantly, while the potent antiviral activity of PSGL-1 has been clearly demonstrated in various complementary model systems, the breadth of PSGL-1 incorporation across genetically diverse viral isolates and clinical isolates has yet to be described. Additionally, the biological activity of virion-incorporated PSGL-1 has also yet to be shown.ResultsHerein we assessed the levels of PSGL-1 on viruses produced through transfection with various amounts of PSGL-1 plasmid DNA (0–250 ng), compared to levels of PSGL-1 on viruses produced through infection of T cell lines and primary PBMC. We found that very low levels of PSGL-1 plasmid DNA (< 2.5 ng/well) were necessary to generate virus models that could closely mirror the phenotype of viruses produced via infection of T cells and PBMC. Unique to this study, we show that PSGL-1 is incorporated in a broad range of HIV-1 and SIV isolates and that virions with incorporated PSGL-1 are detectable in plasma from viremic HIV-1-infected individuals, corroborating the relevance of PSGL-1 in natural infection. Additionally, we show that PSGL-1 on viruses can bind its cognate selectin receptors, P-, E-, and L-selectins. Finally, we show viruses with endogenous levels of PSGL-1 can be captured by P-selectin and transferred to HIV-permissive bystander cells, highlighting a novel role for PSGL-1 in HIV-1 infection. Notably, viruses which contained high levels of PSGL-1 were noninfectious in our hands, in line with previous findings reporting the potent antiviral activity of PSGL-1.ConclusionsOur results indicate that levels of PSGL-1 incorporation into virions can vary widely among model systems tested, and that careful tailoring of plasmid levels is required to recapitulate physiological systems when using pseudovirus models. Taken together, our data suggest that PSGL-1 may play diverse roles in the physiology of HIV-1 infection, particularly due to the functionally active state of PSGL-1 on virion surfaces and the breadth of PSGL-1 incorporation among a wide range of viral isolates.
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33 HIV envelope
34 HIV-1
35 HIV-1 infection
36 HIV-1-infected individuals
37 L-selectin
38 P-selectin
39 P-selectin glycoprotein ligand-1
40 PBMC
41 PSGL-1
42 ResultsHerein
43 SIV isolates
44 T cell lines
45 T cells
46 active state
47 activity
48 amount
49 antiviral activity
50 biological activity
51 breadth
52 broad range
53 bystander cells
54 capture
55 careful tailoring
56 cell lines
57 cells
58 clinical HIV-1
59 clinical isolates
60 cognate receptors
61 complementary model systems
62 data
63 diverse roles
64 diverse viral isolates
65 endogenous levels
66 envelope
67 factors
68 findings
69 hand
70 high levels
71 host restriction factors
72 incorporation
73 individuals
74 infection
75 interaction
76 isolates
77 leukocytes
78 levels
79 ligand 1
80 lines
81 low levels
82 model
83 model system
84 natural infection
85 novel role
86 permissive cells
87 phenotype
88 phenotypes of viruses
89 physiological systems
90 physiology
91 plasma
92 plasmid DNA
93 plasmid levels
94 potent antiviral activity
95 previous findings
96 primary PBMCs
97 range
98 receptors
99 relevance
100 restriction factors
101 results
102 role
103 selectin glycoprotein ligand-1
104 selectin receptors
105 state
106 study
107 subsequent transfer
108 surface
109 system
110 tailoring
111 transfection
112 transfer
113 viral isolates
114 virion surface
115 virions
116 virus
117 virus capture
118 virus model
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