Kaposi’s Sarcoma-Associated Herpesvirus Glycoprotein K8.1 is Dispensable for Viral Entry

Luna, Rafael E.; Zhou, Fuchun; Baghian, A Gharah; Chouljenko, Vladimir N.; Forghani, Bagher; Gao, Shou‐Jiang; Kousoulas, Konstantin G.

doi:10.1100/tsw.2004.164

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“…The attachment assay was performed as described previously 25 . Briefly, cells were incubated with KSHV and spin-inoculated by centrifugation at 4°C and 4122g for 30min.…”

Section: Attachment Assaymentioning

confidence: 99%

“…These interactions are generally thought to result in endocytosis of the viral particle and then membrane fusion from endocytic compartments, as various endocytic routes have been found to be important for productive entry of KSHV and it is sensitive to inhibition of the vacuolar ATPase 14, [16][17][18] . For both KSHV and the related rhesus monkey rhadinovirus (RRV) experiments aimed at ablating certain receptor interactions, such as those with integrins 16,19 or Eph family receptors 11,14,[20][21][22] , mutating receptor interaction sites 12,21 or deleting individual glycoproteins [23][24][25] did not result in complete loss of infectivity, which suggests the existence of additional cellular factors that mediate entry. KSHV and RRV exhibit high similarity with regard to cell tropism, associated disease spectrum and in part receptor usage as both viruses use Eph family receptors 12,14,22 .…”

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confidence: 99%

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Tim-1 and Tim-4 mediate entry of the human Kaposi’s sarcoma-associated herpesvirus and the related rhesus monkey rhadinovirus

Scribano,

Schlagowski,

Liu

et al. 2023

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Kaposi’s sarcoma-associate herpesvirus (KSHV) is a human tumor virus. It is associated with Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. KSHV is known to interact with several different receptors, among them heparan sulfate proteoglycans, Eph family receptors and integrins. We mutated the closely related rhesus monkey rhadinovirus in the known receptor interaction sites for Eph family and Plexin domain containing proteins and found it to still replicate on certain cells. This lytic virus was then used as a selection agent in a genome-wide CRISPR knockout screen, which identified TIM1 and NRP1 as host dependency factors. NRP1 is also host factor for the related Epstein-Barr virus and was recently reported to promote KSHV infection, which we confirm even if it functions with low efficiency on most cells and became functional only after ablation of the Eph receptor interaction. Further analysis through knockout and overexpression demonstrated that Tim-1 and the related Tim-4 are strong mediators of RRV and KSHV infection, in particular in the absence of other receptor interactions and even more pronounced for a KSHV mutant deleted in glycoprotein K8.1. Both Tim-1 and Tim-4 are heavily O-glycosylated phosphatidylserine (PS) receptors. For KSHV in particular, experiments with mutated Tim-1 and comparison to Ebola virus glycoprotein-driven entry indicate that the interaction with Tim-1 occurs through PS-binding by Tim-1 and suggest addition interaction in a PS-independent manner. The mucin-like domain of Tim-1 is critical for receptor function. Usage of Tim proteins for entry is a novelty for herpesviruses and underscores the unique biology of KSHV and RRV.

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“…The attachment assay was performed as described previously 25 . Briefly, cells were incubated with KSHV and spin-inoculated by centrifugation at 4°C and 4122g for 30min.…”

Section: Attachment Assaymentioning

confidence: 99%

mentioning

confidence: 99%

Tim-1 and Tim-4 mediate entry of the human Kaposi’s sarcoma-associated herpesvirus and the related rhesus monkey rhadinovirus

Scribano,

Schlagowski,

Liu

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

Kaposi’s Sarcoma-Associated Herpesvirus Glycoprotein K8.1 is Dispensable for Viral Entry

Cited by 1 publication

References 0 publications

Tim-1 and Tim-4 mediate entry of the human Kaposi’s sarcoma-associated herpesvirus and the related rhesus monkey rhadinovirus

Tim-1 and Tim-4 mediate entry of the human Kaposi’s sarcoma-associated herpesvirus and the related rhesus monkey rhadinovirus

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