The human immunodeficiency virus type 1 envelope confers higher rates of replicative fitness to perinatally transmitted viruses than to nontransmitted viruses.
Selection of a minor viral genotype during perinatal transmission of human Immunodeficiency virus type 1 (HIV-1) has been observed, but there is a lack of information on the correlation of the restrictive transmission with biological properties of the virus, such as replicative fitness. Recombinant viruses expressing the enhanced green fluorescent protein or the Discosoma sp. red fluorescent (DsRed2) protein carrying the V1 to V5 regions of env from seven mother-infant pairs (MIPs) infected by subtype C HIV-1 were constructed, and competition assays were carried out to compare the fitness between the transmitted and nontransmitted viruses. Flow cytometry was used to quantify the frequency of infected cells, and the replicative fitness was determined based on a calculation that takes into account replication of competing viruses in a single infection versus dual infections. Transmitted viruses from five MIPs with the mothers chronically infected showed a restrictive env genotype, and all the recombinant viruses carrying the infants' Env had higher replicative fitness than those carrying the Env from the mothers. This growth fitness is lineage specific and can be observed only within the same MIP. In contrast, in two MIPs where the mothers had undergone recent acute infection, the viral Env sequences were similar between the mothers and infants and showed no further restriction in quasispecies during perinatal transmission. The recombinant viruses carrying the Env from the infants' viruses also showed replication fitness similar to those carrying the mothers' Env proteins. Our results suggest that newly transmitted viruses from chronically infected mothers have been selected to have higher replicative fitness to favor transmission, and this advantage is conferred by the V1 to V5 region of Env of the transmitted viruses. This finding has important implications for vaccine design or development of strategies to prevent HIV-1 transmission.
Kong
Xiaohong
X
Nebraska Center for Virology, and The School of Biological Sciences, University of Nebraska, Lincoln, Nebraska 68583-0900, USA.
West
John T
JT
Zhang
Hong
H
Shea
Danielle M
DM
M'soka
Tendai J
TJ
Wood
Charles
C
D000163:Acquired Immunodeficiency Syndrome / Q000635:transmission*; D005260:Female; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D011247:Pregnancy; D011995:Recombination, Genetic; D014779:Virus Replication; D054299:env Gene Products, Human Immunodeficiency Virus / Q000502:physiology*
D054299:env Gene Products, Human Immunodeficiency Virus
J Virol. 2000 Oct;74(19):9222-33
10982369
J Virol. 2001 Mar;75(5):2194-203
11160723
J Virol. 2006 Jul;80(13):6525-33
16775339
Antimicrob Agents Chemother. 2002 Jun;46(6):1896-905
12019106
J Med Virol. 2006 May;78(5):523-34
16555291
Virology. 2007 Jul 20;364(1):140-6
17395236
Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1721-5
8446584
J Virol. 2003 Mar;77(5):3050-7
12584330
Retrovirology. 2006 Oct 20;3:73
17054795
J Clin Invest. 1994 Jan;93(1):380-90
8282808
Lancet. 1987 Nov 7;2(8567):1094
2890007
AIDS. 2008 Apr 23;22(7):817-24
18427199
Crit Rev Clin Lab Sci. 2005;42(1):1-34
15697169
J Virol. 2003 Aug;77(16):9069-73
12885922
J Gen Virol. 1993 Sep;74 ( Pt 9):1747-56
8376956
J Virol. 2005 Jul;79(14):8979-90
15994792
Science. 2004 Mar 26;303(5666):2019-22
15044802
J Virol. 2008 Apr;82(8):3952-70
18256145
J Virol. 2005 May;79(10):6523-7
15858036
Curr Opin Infect Dis. 2001 Feb;14(1):23-8
11979111
Brief Bioinform. 2004 Jun;5(2):150-63
15260895
J Virol. 2005 Jul;79(14):9006-18
15994794
J Virol. 2005 Jun;79(11):7121-34
15890952
Adv Pharmacol. 2000;49:41-66
11013760
J Virol. 2004 Oct;78(20):11130-41
15452233
Front Biosci. 2006 Sep 01;11:2828-44
16720355
J Virol. 2003 Jan;77(2):1021-38
12502818
Int J Cancer. 2001 Dec 1;94(5):749-52
11745472
Drug Resist Updat. 2002 Dec;5(6):224-33
12531179
BMC Evol Biol. 2006 Mar 23;6:28
16556318
J Clin Invest. 1994 Nov;94(5):2060-7
7962552
J Infect Dis. 1993 Jul;168(1):207-10
8515110
J Virol Methods. 2006 Sep;136(1-2):102-17
16690137
J Virol. 1996 Jul;70(7):4474-83
8676472
J Infect Dis. 2006 Jun 1;193(11):1504-11
16652277
AIDS Res Hum Retroviruses. 2002 Apr 10;18(6):447-60
11958688
J Virol. 2007 Jan;81(2):822-34
17079310
Science. 1992 Feb 28;255(5048):1134-7
1546316
J Virol. 2001 Dec;75(23):11503-14
11689632
Virology. 2007 Jul 5;363(2):447-53
17355886
Retrovirology. 2006 Jul 03;3:40
16817969