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PubMed2001

Gene regulation and host adaptation mechanisms in Candida albicans.

The yeast Candida albicans is a harmless member of the normal microflora on the mucosal surfaces of most healthy persons, but it can cause severe opportunistic infections in immunosuppressed patients. To become a successful human commensal and pathogen, C. albicans has evolved host adaptation mechanisms on different levels. The regulated expression of virulence and other genes in response to environmental signals allows an optimal adaptation to new host niches during the course of an infection. In addition, C. albicans is able to switch between different cell types in a reversible and apparently random fashion. Phenotypic switching involves the coordinated regulation of phase-specific genes, and the resulting generation of selected, pre-programmed cell types may represent an additional strategy to adapt to certain host environments. Finally, C. albicans produces genetically altered variants at a high rate. This microevolution ensures survival when the pathogen encounters new adverse conditions, as exemplified by the development of stable drug-resistant variants under the selection pressure caused by antimycotic therapy. Thus, rather than the possession of single dominant virulence factors, it is its remarkable versatility that makes C. albicans the most important fungal pathogen of humans.

Adaptation, Physiological↗
PubMed2006

NTNG1 mutations are a rare cause of Rett syndrome.

A translocation that disrupted the netrin G1 gene (NTNG1) was recently reported in a patient with the early seizure variant of Rett syndrome (RTT). The netrin G1 protein (NTNG1) has an important role in the developing central nervous system, particularly in axonal guidance, signalling and NMDA receptor function and was a good candidate gene for RTT. We recruited 115 patients with RTT (females: 25 classic and 84 atypical; 6 males) but no mutation in the MECP2 gene. For those 52 patients with epileptic seizure onset in the first 6 months of life, CDKL5 mutations were also excluded. We aimed to determine whether mutations in NTNG1 accounted for a significant subset of patients with RTT, particularly those with the early onset seizure variant and other atypical presentations. We sequenced the nine coding exons of NTNG1 and identified four sequence variants, none of which were likely to be pathogenic. Mutations in the NTNG1 gene appear to be a rare cause of RTT but NTNG1 function demands further investigation in relation to the central nervous system pathophysiology of the disorder.

DNA Mutational Analysis↗
PubMed2003

Little evidence for involvement of MLH3 in colorectal cancer predisposition.

Mutations in the DNA MMR genes MSH2, MLH1, MSH6 and PMS2 underlie a large subset of HNPCC cases, and a hallmark of the tumors is MSI. In many HNPCC families, however, a causative mutation has not been found. Therefore, the involvement of additional, thus far unknown, genes in MSI as well as MSS colorectal tumor predisposition is possible. The role of a relatively recently cloned MMR gene, MLH3, in familial CRC has been studied; but the results appear somewhat conflicting. To further evaluate the role of MLH3 in CRC predisposition, we analyzed 30 Finnish CRC cases for germline mutations by sequencing. These cases were selected from a large series of Finnish CRC patients, to match features previously proposed to associate with MLH3 germline defects. We found 5 missense variants, 4 of which were also found in Finnish cancer-free controls. The only remaining variant does not appear to be an attractive candidate for a disease-associated mutation because the amino acid change is located outside the conserved residues. We also screened for the previously reported variants, including a frameshift change, the most likely pathogenic MLH3 mutation observed so far. The frameshift was not present in the 30 CRC cases or in 700 cancer-free controls. While it is a difficult task to exclude a role of MLH3 in HNPCC, our study could not confirm a role for MLH3 in CRC predisposition.

Carrier Proteins↗
PubMed1996

Molecular studies on bromovirus capsid protein. II. Functional analysis of the amino-terminal arginine-rich motif and its role in encapsidation, movement, and pathology.

The N-terminal region of the brome mosaic bromovirus (BMV) coat protein (CP) contains an arginine-rich motif that is conserved among plant and nonplant viruses and implicated in binding the RNA during encapsidation. To elucidate the functional significance of this conserved motif in the BMV CP, a series of deletions encompassing the arginine-rich motif was introduced into a biologically active clone of BMV RNA3, and their effect on replication, encapsidation, and infection in plants was examined. Analysis of infection phenotypes elicited on Chenopodium quinoa revealed the importance of the first 19 N-proximal amino acids of BMV CP in encapsidation and pathogenicity. Inoculation of C. quinoa with three viable variants of BMV RNA3 lacking the first 11, 14, and 18 N-terminal amino acids of the CP resulted in the development of necrotic local lesions and restricted the spread of infection to inoculated leaves. Progeny analysis from symptomatic leaves revealed that, in each case, virus accumulation was severely affected by the introduced mutations and each truncated CP differed in its ability to package genomic RNA. In contrast to these observations in C. quinoa, none of the CP variants was able to establish either local or systemic infections in barley plants. The intrinsic role played by the N-terminal arginine-rich motif of BMV CP in packaging viral RNAs and the interactions between the host and the truncated CPs in modulating symptom expression and movement are discussed.

Amino Acid Sequence↗
PubMed1986

Similarities and dissimilarities in the structure and expression of viral genomes of various virus strains immunologically related to Marek's disease virus.

Various strains immunologically related to Marek's disease virus (MDV) have been subdivided into three serotypes: serotype 1, pathogenic strains of MDV and attenuated or apathogenic variants derived from them; serotype 2, naturally occurring apathogenic strains of MDV; serotype 3, herpesvirus of turkey (HVT). The viral genome structures of these three serotypes were compared by a simple, practical method using total DNA extracted from virus-infected cells instead of viral DNA purified from virions. The restriction endonuclease-cleavage patterns of serotype 2 viral DNA were found to differ from those of either serotype 1 MDV or serotype 3. Under stringent conditions, no significant DNA homology was detected among the three serotype viruses, except in a restricted portion of these viral genomes. Northern blot hybridization experiments suggested that virus-specific polyadenylated RNA of about 2.4 kilobases was transcribed from a restricted portion showing close homology in these viruses. Southern blot hybridization under less stringent conditions revealed that regions with weak homology were distributed over most of the viral genomes of the three serotypes. Two types of virus-specific glycoproteins, gA and gB, were identified in the immunoprecipitates of the culture medium and cell lysates, respectively, of serotype 2-infected cultures with monoclonal antibodies or hyperimmune antisera cross reactive with serotype 1 MDV and serotype 3 HVT, and detected on the surface of serotype 2-infected cells by the membrane immunofluorescence test. These results indicate a close evolutionary relationship among these three viral serotypes.

Animals↗
PubMed1999

Pathogenic, antigenic and molecular properties of rabbit haemorrhagic disease virus (RHDV) isolated from vaccinated rabbits: detection and characterization of antigenic variants.

Rabbit haemorrhagic disease virus (RHDV) isolates were obtained from several animals previously vaccinated with an inactivated vaccine. Seven isolates were analyzed by immunological and molecular biological methods and compared to reference strains. Antigenic characterization with monoclonal antibodies as well as haemagglutination assays demonstrated considerable differences between individual isolates. However, sequencing of the capsid protein genes revealed a high degree of homology between five of these isolates and the reference strain FRG. In contrast, two isolates specified remarkably different capsid proteins with a degree of variation not observed so far in RHDV. Amino acid alterations were found clustered between residues 301 and 328 (region C), 344 and 434 (region E) and also in the 3' region of the capsid protein gene. Interestingly, experimental vaccination of rabbits followed by challenge with the heterologous variant strains showed restricted cross-protection against one of the strains. In summary, we found a level of antigenic variation not detected in RHDV so far, and describe two distinct new antigenic variants.

Amino Acid Sequence↗
PubMed2005

The role of viral fitness in HIV pathogenesis.

The development of clinical symptoms, and clinical progression among persons infected with HIV-1 is the manifestation of the effects of the pathogenic viral life cycle of HIV-1. Individual variants of HIV-1 vary widely in features that determine viral fitness and virulence. HIV-1 exploits host antiviral responses, the APOBEC3G cytidine deaminase, and the low-fidelity HIV-1 reverse transcriptase, to ensure new variants with novel phenotypic features are continually present for expansion in response to changing conditions in the host, such as immune responses, or antiretroviral therapy. This high-level variance has led to a wide range in observed fitness and virulence, across strains of HIV-1. The HIV-1 pol replication capacity assay (pol RC) measures features of viral fitness, associates with elevated CD4+ T-cell counts, yet is not strongly associated with HIV-1 RNA levels. The biological basis for elevated CD4+ T-cell counts among those carrying a virus of low pol RC may be because of lowered virus infectivity, or restricted tissue replication.

APOBEC-3G Deaminase↗
PubMed1998

Detection of mutator subpopulations in Salmonella typhimurium LT2 by reversion of his alleles.

Defects in the methyl-directed mismatch repair lead to both the hypermutability phenotype and removal of a barrier to genetic exchange between species. Mutator bacteria carrying such defects occur frequently among bacterial pathogens, suggesting that subpopulations of mutators are contained within pathogen clones and give rise to the genetic variants that are acted upon by selective forces to allow survival or successful infection. We report here on the detection of the mutator subpopulation in Salmonella typhimurium and determination of its frequency in laboratory cultures. The analysis involved screening for mutators among revertants of S. typhimurium histidine auxotrophs selected for the His+ phenotype, since the frequency of mutators is expected to be increased in the selected mutant population they helped to spawn. The increases in spontaneous reversion of histidine mutations were first measured in isogenic strains carrying mismatch repair-defective mutH, mutL, mutS, or uvrD alleles, relative to their mismatch repair-proficient counterparts. Screening for the mutator phenotype in nearly 12,000 revertants of repair-proficient strains carrying his mutations highly stimulated for reversion in mutator backgrounds, the base substitution in hisG428 and frameshift in hisC3076, yielded five mutator strains (0.04%). The his+ reversion mutations contained within the newly-arisen mutator strains were characteristic of the predominant nucleotide changes expected in such mutators, as assessed by comparison with the spectra for reversion events in wild-type and mismatch correction-defective backgrounds. The results show that subpopulations of mutators, residing in normal populations at a finite frequency, can be culled from the culture by strong selection for a required phenotype. We calculate that the frequency of mutators in the unselected population of S. typhimurium is 1-4x10-6, an incidence 10-fold lower than that expected based on studies of laboratory cultures of Escherichia coli.

Alleles↗
PubMed2006

Fumonisin production in the maize pathogen Fusarium verticillioides: genetic basis of naturally occurring chemical variation.

Fumonisins are polyketide-derived mycotoxins produced by the maize pathogen Fusarium verticillioides. Previous analyses identified naturally occurring variants of the fungus that are deficient in fumonisin C-10 hydroxylation or that do not produce any fumonisins. In the current study, gene deletion and genetic complementation analyses localized the C-10 hydroxylation deficiency to a cytochrome P450 monooxygenase gene in the fumonisin biosynthetic gene (FUM) cluster. Sequence analysis indicated that the hydroxylation deficiency resulted from a single nucleotide insertion that caused a frame shift in the coding region of the gene. Genetic complementation localized the fumonisin-nonproduction phenotype to the polyketide synthase gene in the FUM cluster, and sequence analysis indicated that the nonproduction phenotype resulted from a nucleotide substitution, which introduced a premature stop codon in the coding region. These results provide the first direct evidence that altered fumonisin production phenotypes of naturally occurring F. verticillioides variants can result from single point mutations in the FUM cluster.

Fumonisins↗
PubMed2025

Mitochondrial dysfunction in MED13 variant-associated disease: a case of infantile spasms, cardiomyopathy and hepatomegaly.

Here we report a de novo heterozygous MED13 variant (c.2503C>T, p.Pro835Ser) in an infant presenting with infantile spasms, hypertrophic cardiomyopathy and hepatomegaly. Autopsy revealed mitochondrial abnormalities in cardiac and hepatic tissues, with reduced respiratory chain complex activity. This is the first case report linking a MED13 variant to systemic mitochondrial dysfunction, suggesting a novel pathogenic mechanism.

Journal Article↗
PubMed1998

Hepatitis C virus and GB virus C/hepatitis G virus viremia in Swedish blood donors with different alanine aminotransferase levels.

BACKGROUND: Hepatitis C virus (HCV) is a known blood-borne hepatotropic virus for which antibody screening of blood donors is universally practiced. The newly identified GB virus C (GBV-C) and its strain variant hepatitis G virus (HGV) are of unknown pathogenic significance, and screening of blood donors for this agent has not yet been implemented. Polymerase chain reaction (PCR) is the most sensitive method for detecting HCV viremia and is the only method presently available for the diagnosis of GBV-C/HGV infection. STUDY DESIGN AND METHODS: RNA extracts of sera from 577 anti-HCV-negative blood donors (393 with elevated alanine aminotransferase [ALT] levels, 184 with normal ALT levels) were tested with nested PCR for HCV and GBV-C/HGV directed at the 5'-noncoding regions of the two viruses. RESULTS: One donor with elevated ALT was HCV PCR positive. This donor was anti-HCV negative when recruited to the study but subsequently developed anti-HCV. Of the 19 donors with GBV-C/HGV viremia in the series as a whole, 16 belonged to the group with elevated ALT levels and 3 to the group with normal ALT levels; the group difference in prevalence was nonsignificant (4.1% [16/393] vs. 1.6% [3/184; p = 0.20]). Phylogenetic analysis showed 16 of the GBV-C/HGV isolates to be classifiable as subtype 2a and three as subtype 2b. At follow-up 3 to 5 years later, 11 of 18 donors were still viremic. CONCLUSION: There was no significant difference in GBV-C/HGV viremia in the group with elevated ALT levels and the group with normal ALT levels. The frequency and subtype distribution in the present series were similar to those in other Western countries.

Adolescent↗
PubMed1993

Deleting two amino acids in glycoprotein gI of pseudorabies virus decreases virulence and neurotropism for pigs, but does not affect immunogenicity.

The virulence, pathogenicity and immunogenicity of two pseudorabies virus (PRV) variants were investigated in 3-week-old pigs that had been intranasally infected. Variant M303 (delta 125,126) lacked amino acids valine (125) and cysteine(126) in an immunodominant antigenic region of glycoprotein I (gI) containing two discontinuous antigenic domains, whereas M304 (delta 59,60) lacked amino acids glycine(59) and aspartic acid(60) in a continuous antigenic domain. M303 (delta 125,126) was not virulent for pigs, but M304 (delta 59,60) was as virulent as wild-type PRV: all pigs died within 8 days of infection. Both gI mutant viruses replicated in the oropharyngeal mucosa, although M304 (delta 59,60) replicated to higher virus titres than M303 (delta 125,126), and virus was recovered from various tissues. However, in contrast to M304 (delta 59,60), M303 (delta 125,126) was not recovered from any central nervous system (CNS) tissues examined. Thus, the tendency of PRV to locate in the CNS was markedly reduced by deleting amino acids valine(125) and cysteine(126) of gI. Pigs immunized with M303 were completely protected against challenge infection; no clinical signs of disease were detected, no virus was shed, and no secondary antibody response was detected. Thus, deleting amino acids valine(125) and cysteine(126) in gI decreases virulence and neurotropism and does not affect immunogenicity.

Amino Acids↗
PubMed2001

Dyslipidemia in early second trimester is mainly a feature of women with early onset pre-eclampsia.

OBJECTIVE: To investigate whether hypertriglyceridemic dyslipidemia is a risk factor for either early or late onset pre-eclampsia. DESIGN: Prospective cohort study and nested case-control study. SETTING: Aker Hospital: a university hospital with all levels of obstetric care. PARTICIPANTS: 2,157 Caucasian pregnant women. METHODS: Blood samples were obtained from non-fasting subjects at 18 weeks of gestation. All samples were analysed for triglycerides, total-cholesterol, high density lipoproteins cholesterol and non-high density lipoproteins cholesterol. ApoB-100 were analysed in pre-eclamptic women and in 3:1 matched controls. The cohort data were analysed by multiple logistic regression and the case-control data by conditional logistic regression. MAIN OUTCOME MEASURES: Adjusted odds ratios of early and late onset pre-eclampsia according to early second trimester serum concentration levels of lipids and ApoB-100. RESULTS: Eighteen women developed early onset pre-eclampsia and 53 women developed late onset pre-eclampsia. In the cohort model, women with triglycerides above 2.4mmol/L had increased risk (OR 5. 1; 95% CI 1.1-23.1) of early onset pre-eclampsia compared with those with triglycerides levels < or = 1.5mmol/L. For women with high triglycerides: non-high density lipoproteins cholesterol ratios (>90 centile) the OR (95% CI) for early onset pre-eclampsia was 7.1 (2.3-22.0) compared with those with low ratios (< or = 50 centile). Similar associations were found in the case control model. We found no associations between plasma lipids and risk of late onset pre-eclampsia. CONCLUSIONS: Hypertriglyceridemic dyslipidemia before 20 weeks of gestation is associated with the risk of developing early but not late onset pre-eclampsia, giving support to the contention that these two variants of the disease are at least partly pathogenically different.

Adult↗
PubMed2006

Modification of the trypsin-dependent cleavage activation site of the human metapneumovirus fusion protein to be trypsin independent does not increase replication or spread in rodents or nonhuman primates.

The contribution of cleavage activation of the fusion F protein of human metapneumovirus (HMPV) to replication and pathogenicity in rodents and nonhuman primates was investigated. Recombinant HMPVs were generated in which the naturally occurring trypsin-dependent cleavage sequence (R-Q-S-R downward arrow) was replaced by each of three sequences whose cleavage in vitro does not depend upon added trypsin. Two of these were multibasic sequences derived from avian metapneumovirus type A (R-R-R-R) or type C (R-K-A-R), with the former containing the consensus furin protease cleavage motif (R-X-R/K-R downward arrow). The third one (R-Q-P-R) was derived from a recently described trypsin independent HMPV isolate (J. H. Schickli, J. Kaur, N. Ulbrandt, R. R. Spaete, and R. S. Tang, J. Virol. 79:10678-10689, 2005). To preclude the possibility of conferring even greater virulence to this significant human pathogen, the modifications were done in an HMPV variant that was attenuated by the deletion of two of the three envelope glycoproteins, SH and G. Each of the introduced cleavage sequences conferred trypsin independent F cleavage and growth to HMPV in vitro. However, they differed in the efficiency of trypsin independent growth and plaque formation in vitro: R-R-R-R > R-K-A-R > R-Q-P-R > R-Q-S-R. The R-R-R-R mutant was the only one whose growth in vitro was not augmented by added trypsin, indicative of highly efficient trypsin independent cleavage. When inoculated intranasally into hamsters, there was essentially no difference in the magnitude of replication in the upper or lower respiratory tract between the mutants, and virus was not detected in organs outside of the respiratory tract. Evaluation of the most cleavage-efficient mutant, R-R-R-R, in African green monkeys showed that there was no detectable change in the magnitude of replication in the upper and lower respiratory tract or in immunogenicity and protective efficacy against HMPV challenge. These results suggest that cleavage activation is not a major determinant of HMPV virulence.

Amino Acid Sequence↗
PubMed2002

Increased CCR5 affinity and reduced CCR5/CD4 dependence of a neurovirulent primary human immunodeficiency virus type 1 isolate.

Most human immunodeficiency virus type 1 (HIV-1) viruses in the brain use CCR5 as the principal coreceptor for entry into a cell. However, additional phenotypic characteristics are necessary for HIV-1 neurotropism. Furthermore, neurotropic strains are not necessarily neurovirulent. To better understand the determinants of HIV-1 neurovirulence, we isolated viruses from brain tissue samples from three AIDS patients with dementia and HIV-1 encephalitis and analyzed their ability to induce syncytia in monocyte-derived macrophages (MDM) and neuronal apoptosis in primary brain cultures. Two R5X4 viruses (MACS1-br and MACS1-spln) were highly fusogenic in MDM and induced neuronal apoptosis. The R5 viruses UK1-br and MACS2-br are both neurotropic. However, only UK1-br induced high levels of fusion in MDM and neuronal apoptosis. Full-length Env clones from UK1-br required lower CCR5 and CD4 levels than Env clones from MACS2-br to function efficiently in cell-to-cell fusion and single-round infection assays. UK1-br Envs also had a greater affinity for CCR5 than MACS2-br Envs in binding assays. Relatively high levels of UK1-br and MACS2-br Envs bound to CCR5 in the absence of soluble CD4. However, these Envs could not mediate CD4-independent infection, and MACS2-br Envs were unable to mediate fusion or infection in cells expressing low levels of CD4. The UK1-br virus was more resistant than MACS2-br to inhibition by the CCR5-targeted inhibitors TAK-779 and Sch-C. UK1-br was more sensitive than MACS2-br to neutralization by monoclonal antibodies (2F5 and immunoglobulin G1b12 [IgG1b12]) and CD4-IgG2. These results predict the presence of HIV-1 variants with increased CCR5 affinity and reduced dependence on CCR5 and CD4 in the brains of some AIDS patients with central nervous system disease and suggest that R5 variants with increased CCR5 affinity may represent a pathogenic viral phenotype contributing to the neurodegenerative manifestations of AIDS.

AIDS Dementia Complex↗
PubMed1983

Synthetic peptide immunogens as vaccines.

Synthetic peptide immunogens have been shown to elicit antibodies that can react with full-length proteins containing that peptide. Such antibodies are directed against a specific region of the protein chosen in advance by the investigator and so have a predetermined specificity. In basic research, these antibodies are useful in identifying the protein product of an open reading frame, localizing the gene product to particular cells or subcellular organelles, identifying the enzymatic function of a protein product, following the fate of particular regions of a product through protein maturation processes, analyzing the expression of exons following DNA rearrangements and RNA splicing, and purifying the protein by immunoaffinity chromatography techniques. In medicine, such antibodies may provide reagents for passive vaccination, antitoxin therapy, and targeted immunotherapy of neoplasia. The peptides themselves may be used as synthetic vaccines. The immediate future of the synthetic peptide immunogen in medicine is clear--the promise demonstrated in the laboratory must be reduced to safe application in the hospital. Two barriers to this are the selection of precisely the best peptide and the selection of the proper adjuvant. Currently, a brute force approach is utilized to find the best peptide for eliciting the desired antibodies. This is clearly a problem when the pathogenic organism is assayable only in man. Possibly, by combining studies on the antigenicity of the pathogenic organism with an analysis of naturally occurring variants that alter its immunogenicity, peptide selection will be made easier. Also, since the adjuvants and carriers used in the laboratory are in general too harsh for widespread use in humans and animals, much work needs to be done to find suitable adjuvants and carriers. Nonetheless, now that the major conceptual hurdle to synthetic peptide vaccines has been cleared (that is, it is not necessary to reproduce conformation exactly), it should be relatively straightforward to solve the remaining problems.

Animals↗
PubMed2005

Evolutionary conservation analysis increases the colocalization of predicted exonic splicing enhancers in the BRCA1 gene with missense sequence changes and in-frame deletions, but not polymorphisms.

INTRODUCTION: Aberrant pre-mRNA splicing can be more detrimental to the function of a gene than changes in the length or nature of the encoded amino acid sequence. Although predicting the effects of changes in consensus 5' and 3' splice sites near intron:exon boundaries is relatively straightforward, predicting the possible effects of changes in exonic splicing enhancers (ESEs) remains a challenge. METHODS: As an initial step toward determining which ESEs predicted by the web-based tool ESEfinder in the breast cancer susceptibility gene BRCA1 are likely to be functional, we have determined their evolutionary conservation and compared their location with known BRCA1 sequence variants. RESULTS: Using the default settings of ESEfinder, we initially detected 669 potential ESEs in the coding region of the BRCA1 gene. Increasing the threshold score reduced the total number to 464, while taking into consideration the proximity to splice donor and acceptor sites reduced the number to 211. Approximately 11% of these ESEs (23/211) either are identical at the nucleotide level in human, primates, mouse, cow, dog and opossum Brca1 (conserved) or are detectable by ESEfinder in the same position in the Brca1 sequence (shared). The frequency of conserved and shared predicted ESEs between human and mouse is higher in BRCA1 exons (2.8 per 100 nucleotides) than in introns (0.6 per 100 nucleotides). Of conserved or shared putative ESEs, 61% (14/23) were predicted to be affected by sequence variants reported in the Breast Cancer Information Core database. Applying the filters described above increased the colocalization of predicted ESEs with missense changes, in-frame deletions and unclassified variants predicted to be deleterious to protein function, whereas they decreased the colocalization with known polymorphisms or unclassified variants predicted to be neutral. CONCLUSION: In this report we show that evolutionary conservation analysis may be used to improve the specificity of an ESE prediction tool. This is the first report on the prediction of the frequency and distribution of ESEs in the BRCA1 gene, and it is the first reported attempt to predict which ESEs are most likely to be functional and therefore which sequence variants in ESEs are most likely to be pathogenic.

Breast Neoplasms↗
PubMedDate not supplied

Malaria in pregnancy: getting to grips with a sticky problem.

In malaria-endemic areas, by young adulthood people have developed functional immunity to malaria. However, during pregnancy this immunity is breached and infection occurs, leading to increased risks for mother and child. In the past this effect has been attributed to nonspecific immunosuppression, but recent research has revealed a specific pathogenic mechanism, involving the adherence of rare parasite variants to the placenta. This commentary explores the current state of research in this area and proposes a model of immune evasion and placental colonization. This model points the way to the development of future therapeutic interventions.

Female↗