Although adeno-associated virus (AAV)-2 has a broad tissue-host range and can transduce a wide variety of tissue types, some cells, such as erythro-megakaryoblastoid cells, are non-permissive and appear to lack the AAV-2 receptor. However, limited studies have been reported with the related dependovirus AAV-3. We have previously cloned this virus, characterized its genome and produced an infectious clone. In this study, the gene for green fluorescent protein (GFP) was inserted into AAV-2- and AAV-3-based plasmids and recombinant viruses were produced. These viruses were then used to transduce haematopoietic cells and the transduction efficiencies were compared. In contrast to recombinant (r) AAV-2, rAAV-3 successfully transduced erythroid and megakaryoblastoid cells, although rAAV-2 was superior in transduction of lymphocyte-derived cell lines. Recently, it was reported that heparan sulphate can act as a receptor of AAV-2. The infectivity of rAAV-2 and rAAV-3 was tested with mutant cell lines of Chinese hamster ovary cells that were defective for heparin or heparan sulphate expression on the cell surface. There was no correlation between the ability of rAAV-2 or rAAV-3 to infect cells and the cell surface expression of heparan sulphate and, although heparin blocked both rAAV-2 and rAAV-3 transduction, the ID50 of rAAV-3 was higher than that of rAAV-2. In addition, virus-binding overlay assays indicated that AAV-2 and AAV-3 bound different membrane proteins. These results suggest not only that there are different cellular receptors for AAV-2 and AAV-3, but that rAAV-3 vectors may be preferred for transduction of some haematopoietic cell types.
AlexanderI. E.,
RussellD. W.,
MillerA. D.1997; Transfer of contaminants in adeno-associated virus vector stocks can mimic transduction and lead to artifactual results. Human Gene Therapy 8:1911–1920
ArellaM.,
GarzonS.,
BergeronJ.,
TijssenP.1990; Physicochemical properties, production, and purification of parvoviruses. In Handbook of Parvoviruses pp 11–30 Edited by
TijssenP.
Boca Raton, FL: CRC Press;
BameK. J.,
EskoJ. D.1989; Undersulfated heparan sulfate in a Chinese hamster ovary cell mutant defective in heparan sulfate N -sulfotransferase. Journal of Biological Chemistry 264:8059–8065
BernsK. I.,
BergoinM.,
BloomM.,
LedermanM.,
MuzyczkaN.,
SieglG.,
TalJ.,
TattersallP.1995; Family Parvoviridae . In Virus Taxonomy. Sixth Report of the International Committee on Taxonomy of Viruses pp 169–178 Edited by
MurphyF. A.,
FauquetC. M.,
BishopD. H. L.,
GhabrialS. A.,
JarvisA. W.,
MartelliG. P.,
MayoM. A.,
SummersM. D.
Vienna & New York: Springer-Verlag;
ChatterjeeS.,
LiW.,
WongC. A.,
Fisher-AdamsG.,
LuD.,
GuhaM.,
MacerJ. A.,
FormanS. J.,
WongK. K.Jr1999; Transduction of primitive human marrow and cord blood-derived hematopoietic progenitor cells with adeno-associated virus vectors. Blood 93:1882–1894
ChioriniJ. A.,
YangL.,
LiuY.,
SaferB.,
KotinR. M.1997; Cloning of adeno-associated virus type 4 (AAV4) and generation of recombinant AAV4 particles. Journal of Virology 71:6823–6833
ErlesK.,
SebokovaP.,
SchlehoferJ. R.1999; Update on the prevalence of serum antibodies (IgG and IgM) to adeno-associated virus (AAV. Journal of Medical Virology 59:406–411
EskoJ. D.,
StewartT. E.,
TaylorW. H.1985; Animal cell mutants defective in glycosaminoglycan biosynthesis. Proceedings of the National Academy of Sciences USA: 82:3197–3201
ItouT.,
MiyamuraK.,
AbeA.,
EmiN.,
TanimotoM.,
TerasakiH.,
ShimadzuM.,
SaitoH.1998; Recombinant adeno-associated virus-mediated gene transfer into human leukemia cell lines. International Journal of Hematology 67:27–35
LebkowskiJ. S.,
McNallyM. M.,
OkarmaT. B.,
LerchL. B.1988; Adeno-associated virus: a vector system for efficient introduction and integration of DNA into a variety of mammalian cell types. Molecular and Cellular Biology 8:3988–3996
LeruezM.,
PallierC.,
VassiasI.,
ElouetJ. F.,
RomeoP.,
MorinetF.1994; Differential transcription, without replication, of non-structural and structural genes of human parvovirus B19 in the UT7/EPO cell line as demonstrated by in situ hybridization. Journal of General Virology 75:1475–1478
MonahanP. E.,
SamulskiR. J.,
TazelaarJ.,
XiaoX.,
NicholsT. C.,
BellingerD. A.,
ReadM. S.,
WalshC. E.1998; Direct intramuscular injection with recombinant AAV vectors results in sustained expression in a dog model of hemophilia. Gene Therapy 5:40–49
MuramatsuS.,
MizukamiH.,
YoungN. S.,
BrownK. E.1996; Nucleotide sequencing and generation of an infectious clone of adeno-associated virus 3. Virology 221:208–217
ParksW. P.,
BoucherD. W.,
MelnickJ. L.,
TaberL. H.,
YowM. D.1970; Seroepidemiological and ecological studies of the adenovirus-associated satellite viruses. Infection and Immunity 2:716–722
PodsakoffG.,
WongK. K.Jr,
ChatterjeeS.1994; Efficient gene transfer into nondividing cells by adeno-associated virus-based vectors. Journal of Virology 68:5656–5666
PonnazhaganS.,
WangX.-S.,
WoodyM. J.,
LuoF.,
KangL. Y.,
NallariM. L.,
MunshiN. C.,
ZhouS. Z.,
SrivastavaA.1996; Differential expression in human cells from promoter p6 of human parvovirus B19 following plasmid transfection and recombinant adeno-associated virus 2 (AAV) infection: human megakaryocytic leukaemia cells are non-permissive for AAV infection. Journal of General Virology 77:1111–1122
QingK.,
MahC.,
HansenJ.,
ZhouS.,
DwarkiV.,
SrivastavaA.1999; Human fibroblast growth factor receptor 1 is a co-receptor for infection by adeno-associated virus 2. Nature Medicine 5:71–77
RutledgeE. A.,
HalbertC. L.,
RussellD. W.1998; Infectious clones and vectors derived from adeno-associated virus (AAV) serotypes other than AAV type 2. Journal of Virology 72:309–319
SamulskiR. J.,
ChangL. S.,
ShenkT.1989; Helper-free stocks of recombinant adeno-associated viruses: normal integration does not require viral gene expression. Journal of Virology 63:3822–3828
ShimomuraS.,
WongS.,
BrownK. E.,
KomatsuN.,
KajigayaS.,
YoungN. S.1993; Early and late gene expression in UT-7 cells infected with B19 parvovirus. Virology 194:149–156
TisdaleJ. F.,
DunbarC. E.,
GoodmanS. A.1998; Gene therapy for hematological disorders, HIV infection, and cancer. In Wintrobe’s Clinical Hematology pp 2178–2208 Edited by
LeeG. R.,
FoersterJ.,
GreerR.,
LukensJ.,
RodgersG.,
ParaskevasF.
Baltimore: Williams & Wilkins;
VeomettG.,
KuszynskiC.,
KazakoffP.,
RizzinoA.1989; Cell density regulates the number of cell surface receptors for fibroblast growth factor. Biochemical and Biophysical Research Communications 159:694–700
ZhouS. Z.,
CooperS.,
KangL. Y.,
RuggieriL.,
HeimfeldS.,
SrivastavaA.,
BroxmeyerH. E.1994; Adeno-associated virus 2-mediated high efficiency gene transfer into immature and mature subsets of hematopoietic progenitor cells in human umbilical cord blood. Journal of Experimental Medicine 179:1867–1875