Transmission of Human Immunodeficiency Virus Type 1 (HIV-1) from Mother to Child Correlates with Viral Phenotype

doi:10.1006/viro.1993.1637

Virology

Volume 197, Issue 2, December 1993, Pages 624-629

https://doi.org/10.1006/viro.1993.1637 Get rights and content

Abstract

The aim of this study was to investigate if the risk of mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) is influenced by the biological phenotype of the mother's virus. Virus isolates from 30 HIV-1 infected mothers and 12 infected children born to these mothers were analyzed for replication on several cell lines (Jurkat-tat, Jurkat, CEM, U937 clone 2, and MT-2). We show that mothers who harbor virus able to replicate in cell lines (rapid/high virus) have a significantly higher risk to infect their children than mothers with slow/low virus (P = 0.017). Children born to mothers with rapid/high viruses can be infected by slow/low as well as rapid/high viruses, while mothers with slow/low virus appear to transmit slow/low virus in every case. Our study shows that the biological phenotype of the mother's virus may serve as a complementary marker to CD4+ lymphocyte counts and p24 antigenemia in predicting the risk of transmission of HIV-1 to the child.

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Cited by (127)

The evolution of hiv-1 interactions with coreceptors and mannose C-type lectin receptors
2015, Progress in Molecular Biology and Translational Science
Citation Excerpt :
Moreover, several strains of CXCR4-using SHIVs readily infect macaques via different routes (reviewed in Ref. 51). Although R5 viruses are predominately detected in children infected by their mothers, it is not uncommon that CXCR4-using strains are identified early after birth.52,53 Thus, the transmission of CXCR4-using viruses appears to be more frequent in vertical transmission than in other routes of transmission (reviewed in Ref. 54).
The phenotype of human immunodeficiency virus type 1 (HIV-1) commonly evolves between and within infected individuals, at virus transmission, and during disease progression. This evolution includes altered interactions between the virus and its coreceptors, i.e., chemokine receptors, as well as mannose C-type lectin receptors (CLRs). Transmitted/founder viruses are predominantly restricted to CCR5, whereas the subsequent intrapatient evolution of HIV-1 coreceptor use during progressive disease can be subdivided into two distinct pathways. Accordingly, the CCR5-restricted virus population is either gradually replaced by virus variants able to use CXCR4 or evolves toward an altered, more flexible use of CCR5. Despite a strong dependency on these coreceptors for host cell entry, HIV-1 also interacts with other cell surface molecules during target cell attachment, including the CLRs. The virus interaction with the CLRs may result either in the efficient transfer of virus to CD4⁺ T cells or in the degradation of the virus in endosomal compartments. The determinants of the diverse outcomes depend on which CLR is engaged and also on the glycan makeup of the envelope glycoproteins, which may evolve with the strength of the immune pressure during the disease course. With the current clinical introduction of CCR5 antagonists and the development of additional entry inhibitors, knowledge on the evolution and baseline characteristics of HIV-1 interactions with coreceptor and CLR interactions may play important roles for individualized and optimized treatment strategies. This review summarizes our current understanding of the evolution of HIV-1 interactions with these receptors.
HIV-1 envelope-dependent restriction of CXCR4-using viruses in child but not adult untransformed CD4<sup>+</sup> T-lymphocyte lines
2012, Blood
Citation Excerpt :
Thus, the development of a cellular system based on pediatric cells could be potentially useful to study the peculiarity of HIV infection in children and can help to elucidate the pathogenesis of pediatric AIDS. In this regard, as in adults,17 it is well established that HIV-1 infection of children from their mother (either via placenta, blood exchange during delivery, or by breastfeeding40,41) is started in most cases by an R5 monophyletic strain, regardless of the dominant quasispecies in the transmitting mother.8,14,15 However, transmission of CXCR4-using viruses has been also described and associated with rapid disease progression toward AIDS and death in the absence of cART.42
Phytohemagglutin-stimulated child and adult leukocytes equally supported CCR5-dependent (R5) and CXCR4-dependent (X4) HIV-1 replication. In contrast, when phytohemagglutin-stimulated leukocytes from either healthy or congenitally immunodeficient children were cultured on feeder cells, they well supported R5, but not X4 HIV-1 replication, whereas both viruses equally spread in adult cells maintained in similar conditions. Both child and adult cells showed similar levels of proliferation and surface expression of CD4, CCR5, CXCR4, CD25, CD69, and HLA-DR. Lack of X4 HIV-1 replication in child versus adult cells was not caused by a differential expression of several known HIV-1 restriction factors. Similar levels of HIV DNA synthesis occurred in child cells infected with R5 and X4 viruses up to 48 hours after infection when R5 HIV-1 showed a significantly superior capacity to spread in culture than X4 virus. Cultured child cells well supported single round vescicular stomatitis virus-G pseudotyped virus replication, whereas superinfection of R5-infected cells with X4 HIV-1 (or vice versa) rescued the replication of this latter virus. Thus, child cells exposed to feeder cell culture represent a novel model system in which the superior capacity of R5 versus X4 viruses to spread can be investigated in primary, untransformed CD4⁺ cells.
The evolution of human immunodeficiency virus type-1 (HIV-1) envelope molecular properties and coreceptor use at all stages of infection in an HIV-1 donor-recipient pair
2012, Virology
Citation Excerpt :
The main coreceptors used by HIV-1 in vivo are the chemokine receptors CCR5 and CXCR4 (De Roda Husman et al., 1999; Deng et al., 1996; Dragic et al., 1996; Feng et al., 1996). CCR5-using (R5) viruses predominate in the early stages of HIV-1 infection irrespective of the route of transmission (Casper et al., 2002; Husson et al., 1995; Keele et al., 2008; Salazar-Gonzalez et al., 2008; Scarlatti et al., 1993; Van 't Wout et al., 1994) and persist throughout the course of the disease (Connor et al., 1997; Scarlatti et al., 1997; Schuitemaker et al., 1992). The biological properties of R5 viruses commonly evolve throughout the natural course of infection (Jansson et al., 1996, 1999; Koning et al., 2003; Kwa et al., 2003; Repits et al., 2005).
To trace the evolutionary patterns underlying evolution of coreceptor use within a host, we studied an HIV-1 transmission pair involving a donor who exclusively harbored CCR5-using (R5) variants throughout his entire disease course and a recipient who developed CXCR4-using variants. Over time, R5 variants in the donor optimized coreceptor use, which was associated with an increased number of potential N-linked glycosylation sites (PNGS) and elevated V3 charge in the viral envelope. Interestingly, R5 variants that were transmitted to the recipient preserved the viral characteristics of this late stage genotype and phenotype. Following a selective sweep, CXCR4-using variants subsequently emerged in the recipient coinciding with a further increase in the number of PNGS and V3 charge in the envelope of R5 viruses.
Although described in a single transmission pair, the transmission and subsequent persistence of R5 variants with late stage characteristics demonstrate the potential for coreceptor use adaptation at the population level.
Adaptive evolution in perinatal HIV-I
2005, Best Practice and Research: Clinical Obstetrics and Gynaecology
Citation Excerpt :
Some phenotypic characteristics, based on the envelope (external) characteristics of the virus, appear to suggest selective (tropic) processes are involved in mother-to-child transmission of HIV-1, but there are contradictory reports in almost all cases. Rapidly replicating isolates capable of inducing syncytia in T-cell lines are better transmitted71, but viruses with high replication rates in monocyte-derived macrophages59 which are non-syncytium-inducing72 appear to be important too. For the envelope and internal genes studied, a homogenous or diverse population may be detected in the infant early on (Table 4).
The immune–viral dynamics of the transmission of HIV-1 from mother to child are poorly understood, despite 20 years of research. Here we review evidence that the maternal immune response against HIV-1 can select forms of the virus that evade immunity and when transmitted have negative consequences in the child. Moreover, recent studies indicate that when wild-type virus is transmitted, an early immune response in the child can lead to the selection of viral escape forms in the first few months of life. These data suggest that adaptive immune surveillance in both mother and child contributes to the pathogenesis of early perinatal HIV-1. These observations augment our general understanding of the processes that determine the evolution of HIV-1 as it passes from one host to another.
Zidovudine monotherapy and the prevention of mother-to-child HIV-1 transmission
2005, Lancet Infectious Diseases
Amniotic fluid has higher relative levels of lentivirus-specific antibodies than plasma and can contain neutralizing antibodies
2004, Journal of Clinical Virology
Background: The in utero transmission rate of HIV-1 is estimated to be 10–15% in the absence of interventions and breastfeeding. Natural protective mechanisms involving lentivirus-specific antibodies may therefore exist to limit in utero transmission of lentiviruses. Objectives: HIV-1- and SIV-specific immunoglobulin G (IgG) levels in amniotic fluid samples from humans and rhesus macaques were assessed. Study design: HIV-1- and SIV-specific immunoglobulin G levels, relative to total IgG concentrations in amniotic fluid samples from humans and rhesus macaques, were determined using a quantitative Western blotting procedure. Amniotic fluid from rhesus macaques was tested for the ability to neutralize SIV infection of CEMX174 cells. Results: The levels of HIV-1- and SIV-specific immunoglobulin G, relative to total IgG concentrations in amniotic fluid samples from humans and rhesus macaques, were approximately 3–10-fold higher than in plasma. The ability of antibodies in human amniotic fluid samples to neutralize viral infectivity could not be assessed, because zidovidine was present in the samples. Most amniotic fluid samples from rhesus macques not treated with antiretrovirals were able to neutralize SIV infectivity, except for a sample from a SIV positive rhesus whose infant was infected in utero. Conclusions: Active immunity to HIV-1 resulting in virus-specific antibodies in amniotic fluid exists, and may be a natural barrier to in utero infection. This may provide hope for stimulating neutralizing antibody via vaccine design.

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Regular ArticleTransmission of Human Immunodeficiency Virus Type 1 (HIV-1) from Mother to Child Correlates with Viral Phenotype

Abstract

Regular Article
Transmission of Human Immunodeficiency Virus Type 1 (HIV-1) from Mother to Child Correlates with Viral Phenotype