Binding of Adenovirus Capsid to Dipalmitoyl Phosphatidylcholine Provides a Novel Pathway for Virus Entry

Balakireva, Larissa A.; Schoehn, Guy; Thouvenin, Eric; Chroboczek, Jadwiga

doi:10.1128/jvi.77.8.4858-4866.2003

Cited by 51 publications

(48 citation statements)

References 41 publications

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“…Both genetic and acquired deficiencies in pulmonary surfactant cause severe respiratory failure, which is manifest as acute respiratory distress syndrome, pneumonia, or neonatal respiratory distress syndrome (37,38). Surfactant lipids also serve as binding and entry molecules for non-enveloped adenoviruses during common respiratory infections (39). Therefore, the production of surfactant lipids, especially DPPC, is highly regulated in vivo.…”

Section: Discussionmentioning

confidence: 99%

Cloning and Characterization of Mouse Lung-type Acyl-CoA:Lysophosphatidylcholine Acyltransferase 1 (LPCAT1)

Nakanishi

Shindou

Hishikawa

et al. 2006

Journal of Biological Chemistry

218

210

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Section: Discussionmentioning

confidence: 99%

Cloning and Characterization of Mouse Lung-type Acyl-CoA:Lysophosphatidylcholine Acyltransferase 1 (LPCAT1)

Nakanishi

Shindou

Hishikawa

et al. 2006

Journal of Biological Chemistry

218

210

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“…As mentioned earlier, mutation of critical CAR-binding residues of the fiber knob that result in severe impairment of in vitro gene transfer may have little or no effect in vivo, again questioning the role of the fiber-CAR interaction during a natural infection. Interestingly, a CAR-independent uptake pathway in A549 cells has been shown to occur through interactions of the hexons with lung surfactant [Balakireva et al, 2003]. The Ad fiber/CAR interaction has been implicated in viral egress and spread during infection [Walters et al, 2002], and the large amounts of free unencapsidated fiber and penton that are produced and secreted during infection [Trotman et al, 2003] appear to aid in the dissociation of cell-cell interactions and the spread of infection.…”

Section: Adenovirus Binding Entry and Traffickingmentioning

confidence: 99%

Current Advances and Future Challenges in Adenoviral Vector Biology and Targeting

Campos¹,

Barry²

2007

CGT

170

122

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Gene delivery vectors based on Adenoviral (Ad) vectors have enormous potential for the treatment of both hereditary and acquired disease. Detailed structural analysis of the Ad virion, combined with functional studies has broadened our knowledge of the structure/function relationships between Ad vectors and host cells/tissues and substantial achievement has been made towards a thorough understanding of the biology of Ad vectors. The widespread use of Ad vectors for clinical gene therapy is compromised by their inherent immunogenicity. The generation of safer and more effective Ad vectors, targeted to the site of disease, has therefore become a great ambition in the field of Ad vector development. This review provides a synopsis of the structure/function relationships between Ad vectors and host systems and summarizes the many innovative approaches towards achieving Ad vector targeting.

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“…These data demonstrated that TIM-4 was present on neural stem cell-derived exosomes ( Figure 3B). Because exosomes contain PS, Ad5 could potentially bind exosomes through interaction with anionic phospholipids, 13 followed by entry of the Ad/exosome complex by means of interaction with anionic phospholipids. Of important note, we demonstrated that exosome-mediated uptake of Ad5 could be blocked with coincubation of anti-TIM-4 antibody ( Figure 3C).…”

Section: Blockage Of Exosome-mediated Ad Entry By Interfering With T-mentioning

confidence: 99%

“…The interaction of Ad5 with neural stem cell-derived exosomes in Figure 2 is possibly through interaction of the Ad protein, hexon, with the anionic phospholipids. 13 Subsequent entry of the Ad/exosome complex is possible by means of interaction with anionic phospholipid. This interaction allows receptor-independent entry of Ad virus into a CAR-deficient cell line.…”

mentioning

confidence: 99%

Neural stem cell-derived exosomes mediate viral entry

Sims¹,

Gu²,

Krendelchtchikov³

et al. 2014

IJN

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Background Viruses enter host cells through interactions of viral ligands with cellular receptors. Viruses can also enter cells in a receptor-independent fashion. Mechanisms regarding the receptor-independent viral entry into cells have not been fully elucidated. Exosomal trafficking between cells may offer a mechanism by which viruses can enter cells. Methods To investigate the role of exosomes on cellular viral entry, we employed neural stem cell-derived exosomes and adenovirus type 5 (Ad5) for the proof-of-principle study. Results Exosomes significantly enhanced Ad5 entry in Coxsackie virus and adenovirus receptor (CAR)-deficient cells, in which Ad5 only had very limited entry. The exosomes were shown to contain T-cell immunoglobulin mucin protein 4 (TIM-4), which binds phosphatidylserine. Treatment with anti-TIM-4 antibody significantly blocked the exosome-mediated Ad5 entry. Conclusion Neural stem cell-derived exosomes mediated significant cellular entry of Ad5 in a receptor-independent fashion. This mediation may be hampered by an antibody specifically targeting TIM-4 on exosomes. This set of results will benefit further elucidation of virus/exosome pathways, which would contribute to reducing natural viral infection by developing therapeutic agents or vaccines.

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Binding of Adenovirus Capsid to Dipalmitoyl Phosphatidylcholine Provides a Novel Pathway for Virus Entry

Cited by 51 publications

References 41 publications

Cloning and Characterization of Mouse Lung-type Acyl-CoA:Lysophosphatidylcholine Acyltransferase 1 (LPCAT1)

Cloning and Characterization of Mouse Lung-type Acyl-CoA:Lysophosphatidylcholine Acyltransferase 1 (LPCAT1)

Current Advances and Future Challenges in Adenoviral Vector Biology and Targeting

Neural stem cell-derived exosomes mediate viral entry

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