Adeno-Associated Virus Serotype 4 (AAV4) and AAV5 Both Require Sialic Acid Binding for Hemagglutination and Efficient Transduction but Differ in Sialic Acid Linkage Specificity

Nikola Kaludov; Kevin E Brown; Robert W Walters; Joseph Zabner; John A Chiorini

doi:10.1128/JVI.75.15.6884-6893.2001

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Adeno-Associated Virus Serotype 4 (AAV4) and AAV5 Both Require Sialic Acid Binding for Hemagglutination and Efficient Transduction but Differ in Sialic Acid Linkage Specificity

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Adeno-Associated Virus Serotype 4 (AAV4) and AAV5 Both Require Sialic Acid Binding for Hemagglutination and Efficient Transduction but Differ in Sialic Acid Linkage Specificity

Nikola Kaludov, Kevin E Brown, Robert W Walters, Joseph Zabner and John A Chiorini

Journal of virology, Vol.75(15), pp.6884-6893

08/2001

DOI: 10.1128/JVI.75.15.6884-6893.2001

PMCID: PMC114416

PMID: 11435568

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Abstract

Adeno-associated virus serotype 4 (AAV4) and AAV5 have different tropisms compared to AAV2 and to each other. We recently reported that α2-3 sialic acid is required for AAV5 binding and transduction. In this study, we characterized AAV4 binding and transduction and found it also binds sialic acid, but the specificity is significantly different from AAV5. AAV4 can hemagglutinate red blood cells from several species, whereas AAV5 hemagglutinates only rhesus monkey red blood cells. Treatment of red blood cells with trypsin inhibited hemagglutination for both AAV4 and AAV5, suggesting that the agglutinin is a protein. Treatment of Cos and red blood cells with neuraminidases also indicated that AAV4 bound α2-3 sialic acid. However, resialylation experiments with neuraminidase-treated red blood cells demonstrated that AAV4 binding required α2–3 O-linked sialic acid, whereas AAV5 required N-linked sialic acid. Similarly, resialylation of sialic acid-deficient CHO cells supported this same conclusion. The difference in linkage specificity for AAV4 and AAV5 was confirmed by binding and transduction experiments with cells incubated with either N-linked or O-linked inhibitors of glycosylation. Furthermore, AAV4 transduction was only blocked with soluble α2-3 sialic acid, whereas AAV5 could be blocked with either α2–3 or α2-6 sialic acid. These results suggest that AAV4 and AAV5 require different sialic acid-containing glycoproteins for binding and transduction of target cells and they further explain the different tropism of AAV4 and AAV5.

Virus-Cell Interactions

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Title: Subtitle: Adeno-Associated Virus Serotype 4 (AAV4) and AAV5 Both Require Sialic Acid Binding for Hemagglutination and Efficient Transduction but Differ in Sialic Acid Linkage Specificity
Creators: Nikola Kaludov - Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research
Kevin E Brown - Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research
Robert W Walters - Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research
Joseph Zabner - Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research
John A Chiorini - Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research
Resource Type: Journal article
Publication Details: Journal of virology, Vol.75(15), pp.6884-6893
DOI: 10.1128/JVI.75.15.6884-6893.2001
PMID: 11435568
PMCID: PMC114416
NLM abbreviation: J Virol
ISSN: 0022-538X
eISSN: 1098-5514
Publisher: American Society for Microbiology
Language: English
Date published: 08/2001
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
Record Identifier: 9984094504002771

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