HIV‐1 Tropism and Survival in Vertically Infected Ugandan Infants

Church, Jessica D.; Huang, Wei; Mwatha, Anthony; Toma, Jonathan; Stawiski, Eric; Donnell, Deborah; Guay, Laura; Mmiro, Francis; Musoke, Philippa; Jackson, J. Brooks; Parkin, Neil; Eshleman, Susan H.

doi:10.1086/587492

Cited by 31 publications

(30 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These studies demonstrate that early virus isolates from plasma samples within the first 4 months of life in P and SP infants have marked differences in viral RC. We show that SP infants typically have virus with a low RC, which is consistent with an important influence of viral attenuation on pediatric HIV progression and is consistent with recently published data in D clade infected infants showing an association between viral infectivity and survival during infancy (7). Although in general there was a concordance between measurements of the RC and infectivity determined by replication kinetics and single-cycle infectivity, in some instances this was not the case.…”

Section: Discussionsupporting

confidence: 91%

Replicative Capacity of Human Immunodeficiency Virus Type 1 Transmitted from Mother to Child Is Associated with Pediatric Disease Progression Rate

Prado

Prendergast

Thobakgale

et al. 2010

J Virol

View full text Add to dashboard Cite

Human immunodeficiency virus (HIV)-infected infants in the developing world typically progress to AIDS or death within the first 2 years of life. However, a minority progress relatively slowly. This study addresses the potential contribution of viral factors to HIV disease progression in eight infants selected from a wellcharacterized cohort of C clade HIV-infected infants, monitored prospectively from birth in Durban, South Africa. Three infants were defined as "progressors," and five were defined as "slow progressors." We observed that slow-progressor infants carry HIV isolates with significantly lower replicative capacity compared to virus from progressors. Furthermore, our data suggest a link between the attenuated viral phenotype and HLA-B* 57/5801 epitope-specific Gag mutational patterns of the transmitted virus and not to coreceptor usage or to the presence of Nef deletions or insertions. These data underline the importance of virus-host interactions and highlight the contribution of viral attenuation through Gag-specific CD8 ؉ T-cell escape mutations, among other factors, in the control of pediatric HIV infection.

show abstract

Section: Discussionsupporting

confidence: 91%

Replicative Capacity of Human Immunodeficiency Virus Type 1 Transmitted from Mother to Child Is Associated with Pediatric Disease Progression Rate

Prado

Prendergast

Thobakgale

et al. 2010

J Virol

View full text Add to dashboard Cite

show abstract

“…Unfortunately, no follow-up information was available for the other five subjects in this study. Based on observations in sexual transmission reported here and vertical transmission reported elsewhere, 30 we speculate that in addition to evolution from R5-tropic viruses, the emergence of CXCR4-using viruses during later stages of HIV-1 infection could, in some cases, result from the outgrowth of transmitted CXCR4-using variants.…”

Section: Huang Et Alsupporting

confidence: 68%

Characterization of Human Immunodeficiency Virus Type 1 Populations Containing CXCR4-Using Variants from Recently Infected Individuals

Huang¹,

Toma²,

Stawiski³

et al. 2009

AIDS Research and Human Retroviruses

Self Cite

View full text Add to dashboard Cite

We screened 150 individuals from two recent seroconverter cohorts and found that six (4%) had CXCR4-using viruses. Clonal analysis of these six individuals, along with a seventh individual identified during clinical care as a recent seroconverter, revealed the presence of both X4-and dual-tropic variants in these recently infected adults. The ability of individual CXCR4-using variants to infect cells expressing CD4=CXCR4 or CD4=CCR5 varied dramatically. These data demonstrate that virus populations in some newly infected individuals can consist of either heterogeneous populations containing both CXCR4-using and CCR5-tropic viruses, or homogeneous populations containing only CXCR4-using viruses. The presence of CXCR4-using viruses at early stages of infection suggests that testing for viral tropism before using CCR5 antagonists may be important even in persons with known recent infection. The presence of CXCR4-using viruses in a subset of newly infected individuals could impact the efficacies of vaccine and microbicide strategies that target CCR5-tropic viruses. N umerous studies support the widely accepted viewpoint that CCR5-using (R5-tropic) HIV-1 dominates during the early stages of infection. [1][2][3][4] The protective effect of the CCR5 D32 homozygous mutation against HIV-1 transmission provides compelling support for the highly selective transmission, or outgrowth, of R5-tropic viruses. [5][6][7][8][9] Viruses that use CXCR4 exclusively (X4-tropic) or both CXCR4 and CCR5 (dual-tropic) typically emerge during later stages of disease. [10][11][12] The presence of CXCR4-using viruses (X4-and dual-tropic) has been associated with rapid CD4 þ T cell decline and accelerated disease progression.1,13-16 Whether this decline is a cause or consequence of disease progression is not known. Documented cases of CXCR4-using viruses in individuals recently infected with HIV-1 have raised concern because of the well-established association between CXCR4-using viruses and disease progression. [17][18][19] It is unclear why R5-tropic viruses dominate early HIV-1 infection. Some suggest that a higher density of CCR5-expressing cells at mucosal surfaces or in lymphoid tissues may select for R5-tropic variants during transmission or favor replication after transmission. 20Phenotypic characteristics of CXCR4-using viruses in newly infected individuals, and the frequency with which they occur, have not been well defined. Since the presence of CXCR4-using variants in recent infection may have implications for disease progression, antiretroviral drug treatment, development of vaccines and microbicides, and postexposure prophylaxis, we screened for CXCR4-using viruses in recent seroconverter panels and characterized the coreceptor usage and envelope (env) sequences of individual clones from recently infected subjects who harbored CXCR4-using subtype B viruses. Viruses were classified as R5-, X4-, or DM (dual= mixed)-tropic, based on the phenotypic results determined using the Trofile assay. 21 Briefly, full-length env seque...

show abstract

“…25 An 8% frequency of X4 variants among infants in our study is quite comparable to the 9% observed in a Ugandan study with subtypes A and D-infected infants. Similarly, survival of the infants with the R5 variant was not significantly different from survival of the infants with X4 variants as also observed by Church et al 26 Generally studies have shown that children can progress to AIDS without evidence of X4 virus, and some with X4 variants can remain asymptomatic for more than 1 year. 27 Of the three more recently infected mothers with acute HIV-1 infection, one had R5 genotypes as expected since the X4 genotype is normally associated with advanced disease or is more common in patients receiving antiretroviral therapy.…”

Section: Discussionsupporting

confidence: 72%

Genotypic Analysis of Human Immunodeficiency Virus Type 1envV3 Loop Sequences: Bioinformatics Prediction of Coreceptor Usage Among 28 Infected Mother–Infant Pairs in a Drug-Naive Population

Duri

Soko²,

Gumbo³

et al. 2011

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

We sought to predict virus coreceptor utilization using a simple bioinformatics method based on genotypic analysis of human immunodeficiency virus types 1 (HIV-1) env V3 loop sequences of 28 infected but drug-naive women during pregnancy and their infected infants and to better understand coreceptor usage in vertical transmission dynamics. The HIV-1 env V3 loop was sequenced from plasma samples and analyzed for viral coreceptor usage and subtype in a cohort of HIV-1-infected pregnant women. Predicted maternal frequencies of the X4, R5X4, and R5 genotypes were 7%, 11%, and 82%, respectively. Antenatal plasma viral load was higher, with a mean log(10) (SD) of 4.8 (1.6) and 3.6 (1.2) for women with the X4 and R5 genotypes, respectively, p = 0.078. Amino acid substitution from the conserved V3 loop crown motif GPGQ to GPGR and lymphadenopathy were associated with the X4 genotype, p = 0.031 and 0.043, respectively. The maternal viral coreceptor genotype was generally preserved in vertical transmission and was predictive of the newborn's viral genotype. Infants born to mothers with X4 genotypes were more likely to have lower birth weights relative to those born to mothers with the R5 genotype, with a mean weight (SD) of 2870 (±332) and 3069 (±300) g, respectively. These data show that at least in HIV-1 subtype C, R5 coreceptor usage is the most predominant genotype, which is generally preserved following vertical transmission and is associated with the V3 GPGQ crown motif. Therefore, antiretroviral-naive pregnant women and their infants can benefit from ARV combination therapies that include R5 entry inhibitors following prediction of their coreceptor genotype using simple bioinformatics methods.

show abstract

HIV‐1 Tropism and Survival in Vertically Infected Ugandan Infants

Abstract: 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.

Cited by 31 publications

References 34 publications

Replicative Capacity of Human Immunodeficiency Virus Type 1 Transmitted from Mother to Child Is Associated with Pediatric Disease Progression Rate

Replicative Capacity of Human Immunodeficiency Virus Type 1 Transmitted from Mother to Child Is Associated with Pediatric Disease Progression Rate

Characterization of Human Immunodeficiency Virus Type 1 Populations Containing CXCR4-Using Variants from Recently Infected Individuals

Genotypic Analysis of Human Immunodeficiency Virus Type 1envV3 Loop Sequences: Bioinformatics Prediction of Coreceptor Usage Among 28 Infected Mother–Infant Pairs in a Drug-Naive Population

Contact Info

Product

Resources

About