A 6-amino acid insertion/deletion polymorphism in the mucin domain of TIM-1 confers protections against HIV-1 infection

Biasin, Mara; Sironi, Manuela; Saulle, Irma; Pontremoli, Chiara; Garziano, Micaela; Cagliani, Rachele; Trabattoni, Daria; Caputo, Sergio Lo; Vichi, Francesca; Mazzotta, Francesco; Forni, Diego; Riva, Stefania; Aguilar-Jiménez, Wbeimar; Cedeño, Samandhy; Sánchez, Jorge; Berthou, Christian; Zapata, Wildeman; Rugeles, Marı́a Teresa; Clerici, Mario

doi:10.1016/j.micinf.2016.09.005

Cited by 8 publications

(6 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the massively increased p24 levels in the culture supernatant clearly indicate that the virus is being released well from BAGN-treated cells and that the higher MFI may reflect an increased replication and burst size of infected cells. Interestingly, a recent report showed that TIM-1 variants with a 6-amino acid shorter mucin domain were related with delayed HIV progression and a recent study, using our own cohorts, indicates that losing the mucin domain on TIM-1 is associated with relative protection from HIV infection ( 54 , 55 ). Alternatively, HIV infectivity and cell susceptibility for infection could be increased by more generalizable mechanisms that may affect other viruses as well, including the reduction of the mucin layer associated with membrane glycoproteins, which would increase fusogenicity of the virus or the exposure of the receptors needed for viral infection.…”

Section: Discussionmentioning

confidence: 85%

Benzyl-2-Acetamido-2-Deoxy-α-d-Galactopyranoside Increases Human Immunodeficiency Virus Replication and Viral Outgrowth Efficacy In Vitro

et al. 2018

Self Cite

View full text Add to dashboard Cite

Glycosylation of host and viral proteins is an important posttranslational modification needed to ensure correct function of glycoproteins. For this reason, we asked whether inhibition of O-glycosylation during human immunodeficiency virus (HIV) in vitro replication could affect HIV infectivity and replication rates. We used benzyl-2-acetamido-2-deoxy-α-d-galactopyranoside (BAGN), a compound that has been widely used to inhibit O-glycosylation in several cell lines. Pretreatment and culture of PHA-blast target cells with BAGN increased the percentage of HIV-infected cells (7.6-fold, p = 0.0115), the per-cell amount of HIV p24 protein (1.3-fold, p = 0.2475), and the viral particles in culture supernatants (7.1-fold, p = 0.0029) compared to BAGN-free cultures. Initiating infection with virus previously grown in the presence of BAGN further increased percentage of infected cells (30-fold, p < 0.0001), intracellular p24 (1.5-fold, p = 0.0433), and secreted viral particles (74-fold, p < 0.0001). BAGN-treated target cells showed less CD25 and CCR5 expression, but increased HLA-DR surface expression, which positively correlated with the number of infected cells. Importantly, BAGN improved viral outgrowth kinetics in 66% of the samples tested, including samples from HIV controllers and subjects in whom no virus could be expanded in the absence of BAGN. Sequencing of the isolated virus indicated no skewing of viral quasi-species populations when compared to BAGN-free culture conditions. BAGN also increased virus production in the ACH2 latency model when used together with latency-reversing agents. Taken together, our results identify BAGN treatment as a simple strategy to improve viral outgrowth in vitro and may provide novel insights into host restriction mechanisms and O-glycosylation-related therapeutic targets for HIV control strategies.

show abstract

Section: Discussionmentioning

confidence: 85%

Benzyl-2-Acetamido-2-Deoxy-α-d-Galactopyranoside Increases Human Immunodeficiency Virus Replication and Viral Outgrowth Efficacy In Vitro

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…TIM-1-364aa overexpression significantly promoted the entry and infection of Japanese encephalitis virus compared with the short form of TIM-1 ( 25 ). In human immunodeficiency virus, homozygosity for the short allele of TIM-1 was associated with natural protection from infection and a lower rate of virus replication in CD4 + T lymphocytes ( 28 ). Additionally, TIM-1-364aa was associated with more severe outcome of infection with hepatitis A virus ( 26 , 27 ).…”

Section: Discussionmentioning

confidence: 99%

TIM-1 Augments Cellular Entry of Ebola Virus Species and Mutants, Which Is Blocked by Recombinant TIM-1 Protein

Zhang¹,

Wang

et al. 2022

Microbiol Spectr

View full text Add to dashboard Cite

show abstract

“…Also, a TIM-1 protein containing the 157insMTTTVP insertion bound to HAV more efficiently in binding assays and affected virus uncoating. Moreover, the 6-amino acid deletion provides protection against HIV-1 infection in clinical trials [ 21 , 32 , 33 ]. A 5-amino acid insertion (157ins MTTVP) in TIM-1 made cells more susceptible to viruses than a 6-amino acid 157ins MTTTVP [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have reported that the 6-amino acid insertion (157ins MTTTVP) was associated with several severe diseases [ 31 ]. Polymorphisms of TIM-1 are associated with cell susceptibility to infection by several viruses, including HIV and HAV [ 21 , 32 , 33 ]. However, the role of TIM-1 in JEV infection and if TIM-1 polymorphisms are involved in cells susceptibility to JEV is still unknown.…”

Section: Introductionmentioning

confidence: 99%

TIM-1 Promotes Japanese Encephalitis Virus Entry and Infection

Niu

Jiang

et al. 2018

Viruses

View full text Add to dashboard Cite

Japanese encephalitis virus (JEV) is a mosquito-borne Flavivirus, the leading cause of viral-induced encephalitis. Several host molecules have been identified as the JEV attachment factor; however, the molecules involved in JEV entry remain poorly understood. In the present study, we demonstrate that TIM-1 is important for efficient infection by JEV. Firstly, three TIM-1 variants (V1, V2, and V3) were cloned from A549 cells, and we revealed that only ectopically TIM-1 V2 expression in 293T cells significantly promotes JEV attachment, entry and infection. Point mutation of phosphatidylserine (Ptdser) binding pocket in the TIM-1 IgV domain dampened JEV entry, indicating that TIM-1-mediated JEV infection is Ptdser-dependent. Furthermore, we found the cytoplasmic domain of TIM-1 is also required for enhancing JEV entry. Additionally, knock down of TIM-1 expression in A549 cells impaired JEV entry and infection, but not attachment, suggesting that additional factors exist in A549 cells that allow the virus to bind. In conclusion, our findings demonstrate that TIM-1 promotes JEV infection as an entry cofactor, and the polymorphism of TIM-1 is associated with JEV susceptibility to host cells.

show abstract

A 6-amino acid insertion/deletion polymorphism in the mucin domain of TIM-1 confers protections against HIV-1 infection

Cited by 8 publications

References 18 publications

Benzyl-2-Acetamido-2-Deoxy-α-d-Galactopyranoside Increases Human Immunodeficiency Virus Replication and Viral Outgrowth Efficacy In Vitro

Benzyl-2-Acetamido-2-Deoxy-α-d-Galactopyranoside Increases Human Immunodeficiency Virus Replication and Viral Outgrowth Efficacy In Vitro

TIM-1 Augments Cellular Entry of Ebola Virus Species and Mutants, Which Is Blocked by Recombinant TIM-1 Protein

TIM-1 Promotes Japanese Encephalitis Virus Entry and Infection

Contact Info

Product

Resources

About