HIV-1 tropism and survival in vertically infected Ugandan infants

被引:32
作者
Church, Jessica D. [1 ]
Huang, Wei [2 ]
Mwatha, Anthony [3 ]
Toma, Jonathan [2 ]
Stawiski, Eric [2 ]
Donnell, Deborah [3 ]
Guay, Laura A. [1 ]
Mmiro, Francis [4 ]
Musoke, Philippa [5 ]
Jackson, J. Brooks
Parkin, Neil [2 ]
Eshleman, Susan H. [1 ]
机构
[1] Johns Hopkins Univ, Baltimore, MD USA
[2] Monogram Biosci, San Francisco, CA USA
[3] Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98104 USA
[4] Makerere Univ Johns Hopkins Univ MUJHU Res Collab, Kampala, Uganda
[5] Makerere Univ, Kampala, Uganda
关键词
D O I
10.1086/587492
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. Human immunodeficiency virus type 1 (HIV-1) may utilize the CXCR4 coreceptor (X4 virus), the CCR5 coreceptor (R5 virus), or both (dual/mixed [DM] virus). We analyzed HIV-1 coreceptor tropism in Ugandan infants enrolled in the HIVNET (HIV Network for Prevention Trials) 012 trial. Methods. Plasma or serum was analyzed using a commercial coreceptor tropism assay. HIV env subtype was determined by phylogenetic methods. Results. Tropism results were obtained for 57 samples from infants collected 6-14 weeks after birth. Fifty-two infants had only R5 virus, and 5 had either X4 or DM virus. The mothers of those 5 infants also had X4 or DM virus. In infants, subtype D infection was associated with high-level infectivity in CCR5-bearing cells and also with the detection of X4 or DM strains. High-level infectivity in CCR5-bearing cells was associated with decreased infant survival, but infection with X4 or DM virus was not. HIV clones from infants with DM viral populations showed different patterns of coreceptor use. V3 loop sequence-based algorithms predicted the tropism of some, but not all, env clones. Conclusions. Complex patterns of HIV tropism were found in HIV-infected newborn infants. Subtype D infection was associated with X4 virus and with high-level replication in CCR5-bearing cells. High-level replication of R5 virus was associated with decreased infant survival.
引用
收藏
页码:1382 / 1388
页数:7
相关论文
共 39 条
[1]   HIV-1 subtype D infection is associated with faster disease progression than subtype A in spite of similar plasma HIV-1 loads [J].
Baeten, Jared M. ;
Chohan, Bhavna ;
Lavreys, Ludo ;
Chohan, Vrasha ;
McClelland, R. Scott ;
Certain, Laura ;
Mandaliya, Kishorchandra ;
Jaoko, Walter ;
Overbaugh, Julie .
JOURNAL OF INFECTIOUS DISEASES, 2007, 195 (08) :1177-1180
[2]   Human immunodeficiency virus type 1 tropism for T-lymphoid cell lines: Role of the V3 loop and C4 envelope determinants [J].
Carrillo, A ;
Ratner, L .
JOURNAL OF VIROLOGY, 1996, 70 (02) :1301-1309
[3]   Coreceptor change appears after immune deficiency is established in children infected with different HIV-1 subtypes [J].
Casper, C ;
Navér, L ;
Clevestig, P ;
Belfrage, E ;
Leitner, T ;
Albert, J ;
Lindgren, S ;
Ottenblad, C ;
Bohlin, AB ;
Fenyö, EM ;
Ehrnst, A .
AIDS RESEARCH AND HUMAN RETROVIRUSES, 2002, 18 (05) :343-352
[4]   Link between the X4 phenotype in human immunodeficiency virus type 1-infected mothers and their children, despite the early presence of R5 in the child [J].
Casper, CHE ;
Clevestig, P ;
Carlenor, E ;
Leitner, T ;
Anzén, B ;
Lidman, K ;
Belfrage, E ;
Albert, J ;
Bohlin, AB ;
Navér, L ;
Lindgren, S ;
Fenyö, EM ;
Ehrnst, AC .
JOURNAL OF INFECTIOUS DISEASES, 2002, 186 (07) :914-921
[5]   Assessing chemokine co-receptor usage in HIV [J].
Coakley, E ;
Petropoulos, CJ ;
Whitcomb, JM .
CURRENT OPINION IN INFECTIOUS DISEASES, 2005, 18 (01) :9-15
[6]   MINIMAL REQUIREMENTS FOR THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 V3 DOMAIN TO SUPPORT THE SYNCYTIUM-INDUCING PHENOTYPE - ANALYSIS BY SINGLE AMINO-ACID SUBSTITUTION [J].
DEJONG, JJ ;
DERONDE, A ;
KEULEN, W ;
TERSMETTE, M ;
GOUDSMIT, J .
JOURNAL OF VIROLOGY, 1992, 66 (11) :6777-6780
[7]   Early prognostic indicators in primary perinatal human immunodeficiency virus type 1 infection: Importance of viral RNA and the timing of transmission on long-term outcome [J].
Dickover, RE ;
Dillon, M ;
Leung, KM ;
Krogstad, P ;
Plaeger, S ;
Kwok, S ;
Christopherson, C ;
Deveikis, A ;
Keller, M ;
Stiehm, ER ;
Bryson, YJ .
JOURNAL OF INFECTIOUS DISEASES, 1998, 178 (02) :375-387
[8]   Survival of Ugandan infants with subtype A and D HIV-1 infection (HIVNET 012) [J].
Eshleman, SH ;
Guay, LA ;
Fleming, T ;
Mwatha, A ;
Mracna, M ;
Becker-Pergola, G ;
Musoke, P ;
Mmiro, F ;
Jackson, JB .
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 2002, 31 (03) :327-330
[9]   Selection and fading of resistance mutations in women and infants receiving nevirapine to prevent HIV-1 vertical transmission (HIVNET 012) [J].
Eshleman, SH ;
Mracna, M ;
Guay, LA ;
Deseyve, M ;
Cunningham, S ;
Mirochnick, M ;
Musoke, P ;
Fleming, T ;
Fowler, MG ;
Mofenson, LM ;
Mmiro, F ;
Jackson, JB .
AIDS, 2001, 15 (15) :1951-1957
[10]  
Fitzgibbon JE, 1998, J MED VIROL, V55, P56, DOI 10.1002/(SICI)1096-9071(199805)55:1&lt