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Biomedical subjects

M Louder

Publications and source records attributed to M Louder.

6 recordsLinked to original sources
PubMed2001

Human dendritic cells as targets of dengue virus infection.

Dengue virus infections are an emerging global threat. Severe dengue infection is manifested as dengue hemorrhagic fever and dengue shock syndrome, both of which can be fatal complications. Factors predisposing to complicated disease and pathogenesis of severe infections are discussed. Using immunohistochemistry, immunofluorescence, flow cytometry, and ELISA techniques, we studied the cellular targets of dengue virus infection, at both the clinical (in vivo) and the laboratory (in vitro) level. Resident skin dendritic cells are targets of dengue virus infection as demonstrated in a skin biopsy from a dengue vaccine recipient. We show that factors influencing infection of monocytes/macrophages and dendritic cells are different. Immature dendritic cells were found to be the cells most permissive for dengue infection and maybe early targets for infection. Immature dendritic cells exposed to dengue virus produce TNF-alpha protein. Some of these immature dendritic cells undergo TNF-alpha mediated maturation as a consequence of exposure to the dengue virus.

Biopsy↗
PubMed2000

Construction and biological characterization of infectious molecular clones of HIV-1 subtypes B and E (CRF01_AE) generated by the polymerase chain reaction.

We previously described the use of extended polymerase chain reaction (PCR) to amplify contiguous 9.2-kilobase (kb) single-long terminal repeat (LTR) proviral sequences from HIV-1 genetic subtypes A through G. We now extend these findings by describing a novel vector system to recover infectious molecular clones from long PCR amplicons. Directional ligation of 9.2-kb proviral amplicons into a recovery vector reconstitutes missing LTR sequences, providing candidate molecular clones for infectivity screening. We show that a previously characterized infectious molecular clone of HIV-1 retains its biological properties upon recovery with this strategy. Three additional infectious molecular clones generated, from primary isolates of subtype B (HIV-1(WR27)) and circulating recombinant form 01_AE (subtype E) (HIV-1(CM235)) by subtype-specific LTR reconstitution, displayed biological properties reflecting their cognate parental isolates. This represents the first report of infectious molecular clones from circulating recombinant form 01_AE (subtype E).

Cells, Cultured↗
PubMed1998

Exclusive and persistent use of the entry coreceptor CXCR4 by human immunodeficiency virus type 1 from a subject homozygous for CCR5 delta32.

Individuals who are homozygous for the 32-bp deletion in the gene coding for the chemokine receptor and major human immunodeficiency virus type 1 (HIV-1) coreceptor CCR5 (CCR5 -/-) lack functional cell surface CCR5 molecules and are relatively resistant to HIV-1 infection. HIV-1 infection in CCR5 -/- individuals, although rare, has been increasingly documented. We now report that the viral quasispecies from one such individual throughout disease is homogenous, T cell line tropic, and phenotypically syncytium inducing (SI); exclusively uses CXCR4; and replicates well in CCR5 -/- primary T cells. The recently discovered coreceptors BOB and Bonzo are not used. Although early and persistent SI variants have been described in longitudinal studies, this is the first demonstration of exclusive and persistent CXCR4 usage. With the caveat that the earliest viruses available from this subject were from approximately 4 years following primary infection, these data suggest that HIV-1 infection can be mediated and persistently maintained by viruses which exclusively utilize CXCR4. The lack of evolution toward the available minor coreceptors in this subject underscores the dominant biological roles of the major coreceptors CCR5 and CXCR4. This and two similar subjects (R. Biti, R. Ffrench, J. Young, B. Bennetts, G. Stewart, and T. Liang, Nat. Med. 3:252-253, 1997; I. Theodoreu, L. Meyer, M. Magierowska, C. Katlama, and C. Rouzioux, Lancet 349:1219-1220, 1997) showed relatively rapid CD4+ T-cell declines despite average or low initial viral RNA load. Since viruses which use CXCR4 exclusively cannot infect macrophages, these data have implications for the relative infection of the T-cell compartment versus the macrophage compartment in vivo and for the development of CCR5-based therapeutics.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Rapid disease progression without seroconversion following primary human immunodeficiency virus type 1 infection--evidence for highly susceptible human hosts.

A patient is described who rapidly progressed from primary human immunodeficiency virus (HIV) type 1 infection to death without seroconversion but with consistently high plasma viremia. His asymptomatic sex partner had been HIV-1 seropositive for >8 years prior to transmission. Analysis of viral sequences from these subjects and controls confirmed the transmission event. Although the biologic properties of the patient's virus were unremarkable, he had poor functional immune responses to HIV and an HLA haplotype associated with rapid disease progression. The disparity between immune responses and clinical course in this transmission pair, coupled with infection with an unremarkable HIV-1 isolate, underscores the crucial importance of host factors in HIV-1 pathogenesis.

Adult↗
PubMed1994

Overexpression of nef as a marker for restricted HIV-1 infection of astrocytes in postmortem pediatric central nervous tissues.

In previous studies, using polymerase chain reaction amplification of HIV-1 genes directly from pathologic tissues of children who died with AIDS encephalopathy, we showed that the reading frame of the HIV-1 regulatory nef gene is open, suggesting that the nef protein was expressed. We now show, using immunocytochemistry and in situ hybridization with nef-specific probes in postmortem pediatric CNS tissues, that nef mRNA and protein are present in up to 20% of astrocytes in tissue sections selected for extensive histopathology. By contrast, HIV-1 structural proteins such as gag and their coding mRNAs are present in multinucleated giant cells that harbor productive infection and are the hallmark of HIV-1 infection in the CNS. These findings are consistent with the nonproductive infection of glial cells observed in vitro, and imply that HIV-1 infection of astrocytes is restricted to early regulatory gene products, of which nef is the best target as it is expressed at high levels and is membrane-anchored. In developing central nervous tissues of children, restricted and latent HIV-1 infection of astrocytes may be extensive and contribute significantly to HIV-1 neuropathogenesis.

Aged↗