The rate of hepatitis C virus infection initiation in vitro is directly related to particle density.
To gain a more complete understanding of hepatitis C virus (HCV) entry, we initially assessed the rate at which HCV initiates productive attachment/infection in vitro and discovered it to be slower than most viruses. Since HCV, including cell culture-derived HCV (HCVcc), exhibits a broad-density profile (1.01-1.16 g/ml), we hypothesized that the varying densities of the HCVcc particles present in the inoculum may be responsible for this prolonged entry phenotype. To test this hypothesis, we show that during infection, particles of high density disappeared from the viral inoculum sooner and initiated productive infection faster than virions of low density. Moreover, we could alter the rate of attachment/infection initiation by increasing or decreasing the density of the cell culture medium. Together, these findings demonstrate that the relationship between the density of HCVcc and the density of the extracellular milieu can significantly impact the rate at which HCVcc productively interacts with target cells in vitro.
Sabahi
Ali
A
Department of Microbiology and Immunology, Tulane University Health Sciences Center, New Orleans, LA, USA.
Marsh
Katherine A
KA
Dahari
Harel
H
Corcoran
Peter
P
Lamora
Jennifer M
JM
Yu
Xuemei
X
Garry
Robert F
RF
Uprichard
Susan L
SL
D002460:Cell Line; D002499:Centrifugation, Density Gradient; D003470:Culture Media / Q000737:chemistry; D016174:Hepacivirus / Q000737:chemistry* / Q000254:growth & development / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D019562:Viral Load; D053586:Virus Internalization
D003470:Culture Media
Med Microbiol Immunol. 1993 Dec;182(6):329-34
8121333
J Virol. 2003 Mar;77(5):3181-90
12584342
Baillieres Best Pract Res Clin Gastroenterol. 2000 Apr;14(2):211-28
10890317
Virus Res. 2006 Dec;122(1-2):137-43
16949699
J Virol. 2008 Jun;82(12):5715-24
18367533
Science. 2005 Jul 22;309(5734):623-6
15947137
J Virol. 2002 Mar;76(6):2997-3006
11861865
Science. 1989 Apr 21;244(4902):359-62
2523562
Curr Opin Investig Drugs. 2006 Aug;7(8):727-32
16955684
Arch Virol. 1993;130(3-4):289-300
7686005
Cell Microbiol. 2007 Oct;9(10):2445-56
17517063
Hepatology. 2007 Dec;46(6):1722-31
18000990
PLoS One. 2009 Aug 10;4(8):e6561
19668344
Acta Virol. 1976 Oct;20(5):353-60
11662
Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12766-71
10535997
J Virol. 2007 Apr;81(7):3162-9
17215280
J Biol Chem. 2006 Feb 17;281(7):3909-17
16356932
J Cell Biol. 1989 Dec;109(6 Pt 1):2721-9
2556405
J Viral Hepat. 2008 Dec;15(12):849-54
19087224
J Virol. 2002 Jul;76(14):6919-28
12072493
Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3805-9
16484368
J Virol. 2009 Aug;83(16):8012-20
19515778
Nature. 2009 Feb 12;457(7231):882-6
19182773
J Virol. 2008 Mar;82(5):2120-9
18077707
Virology. 1996 Feb 1;216(1):214-8
8614990
Science. 1999 Jul 2;285(5424):110-3
10390360
EMBO J. 2002 Oct 1;21(19):5017-25
12356718
Virology. 1999 Apr 25;257(1):156-67
10208929
J Virol. 2006 Feb;80(4):1734-41
16439530
Virology. 2004 Feb 5;319(1):152-61
14967496
PLoS Pathog. 2009 Jun;5(6):e1000475
19521536
J Gen Virol. 2009 May;90(Pt 5):1055-1070
19264629
Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):7271-6
12761383
Xenobiotica. 2009 Mar;39(3):205-17
19280519
J Virol. 2007 Jan;81(1):374-83
17050612
J Virol. 2006 Nov;80(22):11082-93
16956932
J Virol. 1970 Apr;5(4):524-32
4195055
J Biol Chem. 2003 Oct 24;278(43):41624-30
12913001
J Med Virol. 1999 Mar;57(3):223-9
10022791
Gastroenterology. 2003 Dec;125(6):1808-17
14724833
Nat Rev Microbiol. 2007 Jun;5(6):453-63
17487147
J Gen Virol. 1980 Apr;47(2):365-72
6245175
Nature. 2007 Apr 12;446(7137):801-5
17325668
Lancet. 2003 Dec 20;362(9401):2095-100
14697814
Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2310-5
16461899
J Virol. 1975 Sep;16(3):621-33
1171993
J Med Virol. 2001 Jul;64(3):334-9
11424123
J Virol. 2006 Jul;80(14):6964-72
16809302
J Med Virol. 1991 Jul;34(3):206-8
1655970
J Biol Chem. 2009 Jun 26;284(26):17657-67
19411248
J Exp Med. 2003 Mar 3;197(5):633-42
12615904
Nat Med. 2005 Jul;11(7):791-6
15951748
J Virol. 2008 Dec;82(24):12020-9
18829747
Microbiol Immunol. 1978;22(7):377-90
30881
J Virol. 2006 Nov;80(22):11074-81
16956946
J Med Virol. 2002 Nov;68(3):335-42
12226819
Med Microbiol Immunol. 1992;181(5):293-300
1335546
J Biol Chem. 2006 Jul 7;281(27):18285-95
16675450
J Virol. 2006 Nov;80(21):10579-90
16928753
J Virol. 1995 Nov;69(11):6712-9
7474081
J Virol. 2000 Nov;74(21):10055-62
11024134
J Virol. 2004 Nov;78(22):12557-65
15507643
J Virol. 2003 Jan;77(1):546-59
12477859
Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9294-9
15939869
Science. 2000 Dec 8;290(5498):1972-4
11110665
Science. 1998 Oct 30;282(5390):938-41
9794763
J Virol. 2009 Feb;83(4):2011-4
19052094
J Biol Chem. 2003 Oct 17;278(42):41003-12
12867431
J Virol. 2006 Dec;80(23):11571-8
17005647
J Hepatol. 2007 Mar;46(3):411-9
17156886
J Virol. 2006 Jun;80(11):5308-20
16699011
J Virol. 2006 Mar;80(5):2418-28
16474148
Anal Biochem. 1987 Apr;162(1):156-9
2440339