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1.
Cell ; 178(1): 190-201.e11, 2019 06 27.
Article En | MEDLINE | ID: mdl-31204101

The placental transfer of maternal IgG is critical for infant protection against infectious pathogens. However, factors that modulate the placental transfer of IgG remain largely undefined. HIV-infected women have impaired placental IgG transfer, presenting a unique "disruption model" to define factors that modulate placental IgG transfer. We measured the placental transfer efficiency of maternal HIV and pathogen-specific IgG in US and Malawian HIV-infected mothers and their HIV-exposed uninfected and infected infants. We examined the role of maternal HIV disease progression, infant factors, placental Fc receptor expression, IgG subclass, and glycan signatures and their association with placental IgG transfer efficiency. Maternal IgG characteristics, such as binding to placentally expressed Fc receptors FcγRIIa and FcγRIIIa, and Fc region glycan profiles were associated with placental IgG transfer efficiency. Our findings suggest that Fc region characteristics modulate the selective placental transfer of IgG, with implications for maternal vaccine design and infant health.


HIV Infections/transmission , HIV/genetics , Immunoglobulin G/blood , Infectious Disease Transmission, Vertical , Placenta/metabolism , Pregnancy Complications, Infectious/virology , Receptors, IgG/metabolism , Cohort Studies , Disease Progression , Female , Glycosylation , HIV Infections/immunology , HIV Infections/virology , Humans , Immunoglobulin Fc Fragments/metabolism , Infant , Infant, Newborn , Malawi , Pregnancy , Pregnancy Complications, Infectious/immunology , United States , Viral Load/genetics
2.
Vaccines (Basel) ; 5(4)2017 Oct 20.
Article En | MEDLINE | ID: mdl-29053596

Research over the past decade has clearly shown that long non-coding RNAs (lncRNAs) are functional. Many lncRNAs can be related to immunity and the host response to viral infection, but their specific functions remain largely elusive. The vast majority of lncRNAs are annotated with extremely limited knowledge and tend to be expressed at low levels, making ad hoc experimentation difficult. Changes to lncRNA expression during infection can be systematically profiled using deep sequencing; however, this often produces an intractable number of candidate lncRNAs, leaving no clear path forward. For these reasons, it is especially important to prioritize lncRNAs into high-confidence "hits" by utilizing multiple methodologies. Large scale perturbation studies may be used to screen lncRNAs involved in phenotypes of interest, such as resistance to viral infection. Single cell transcriptome sequencing quantifies cell-type specific lncRNAs that are less abundant in a mixture. When coupled with iterative experimental validations, new computational strategies for efficiently integrating orthogonal high-throughput data will likely be the driver for elucidating the functional role of lncRNAs during viral infection. This review highlights new high-throughput technologies and discusses the potential for integrative computational analysis to streamline the identification of infection-related lncRNAs and unveil novel targets for antiviral therapeutics.

3.
Genome Announc ; 4(2)2016 Apr 21.
Article En | MEDLINE | ID: mdl-27103725

ITALIC! Aeromicrobium erythreumNRRL B-3381 has a 3,629,239-bp circular genome that has 72% G+C content. There are at least 3,121 coding sequences (CDSs), two rRNA gene operons, and 47 tRNAs. The genome and erythromycin ( ITALIC! ery) biosynthetic gene sequences provide resources for metabolic and combinatorial engineering of polyketides.

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