Donald E. Mosier

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The pressing need for a better experimental system for AIDS research has brought into sharp focus the shortcomings of available animal models and the practical and ethical limitations of studies of immune responses and viral pathogenesis in humans. Current studies of the human immune responses are limited to relatively restrictive in vivo experiments and(More)
Human immunodeficiency virus type 1 (HIV-1) entry into target cells is mediated by the virus envelope binding to CD4 and the conformationally altered envelope subsequently binding to one of two chemokine receptors. HIV-1 envelope glycoprotein (gp120) has five variable loops, of which three (V1/V2 and V3) influence the binding of either CCR5 or CXCR4, the(More)
The natural evolution of human immunodeficiency virus type 1 infection often includes a switch in coreceptor preference late in infection from CCR5 to CXCR4, a change associated with expanded target cell range and worsened clinical prognosis. Why coreceptor switching takes so long is puzzling, since it requires as few as one to two mutations. Here we report(More)
Human immunodeficiency virus type 1 (HIV-1) infects target cells by binding to CD4 and a chemokine receptor, most commonly CCR5. CXCR4 is a frequent alternative coreceptor (CoR) in subtype B and D HIV-1 infection, but the importance of many other alternative CoRs remains elusive. We have analyzed HIV-1 envelope (Env) proteins from 66 individuals infected(More)
Chemokine receptors are found on cell surfaces and promote cellular migration by chemotaxis. The CC chemokine receptor 5 (CCR5) is used by the human immunodeficiency virus (HIV) to infect cells. Strategies that target human CCR5 are therefore being developed to prevent and treat HIV infection. Antiviral strategies that target a host element necessary for(More)
New prevention strategies for use in developing countries are urgently needed to curb the worldwide HIV/AIDS epidemic. The N-terminally modified chemokine PSC-RANTES is a highly potent entry inhibitor against R5-tropic HIV-1 strains, with an inhibitory mechanism involving long-term intracellular sequestration of the HIV coreceptor, CCR5. PSC-RANTES is fully(More)
The envelope gene (env) of human immunodeficiency virus type 1 (HIV-1) undergoes rapid divergence from the transmitted sequence and increasing diversification during the prolonged course of chronic infection in humans. In about half of infected individuals or more, env evolution leads to expansion of the use of entry coreceptor from CCR5 alone to CCR5 and(More)
Previous studies of HIV-1 variants transmitted from mother-to-infant have focused primarily on computational analyses of partial envelope gene sequences, rather than analyses of functional envelope variants. There are very few examples of well-characterized functional envelope clones from mother-infant pairs, especially from envelope variants representing(More)
BACKGROUND During the years preceding this study, we noticed a relatively unusual high number of individuals with elevated alanine aminotransferase (ALT) levels in O'Brien, a small rural town in Argentina. Moreover, four individuals from this town underwent liver transplantation owing to hepatitis C virus (HCV)-induced liver cirrhosis. These findings(More)
We have shown that a mixture of murine leukemia viruses (MuLV) causes the acute onset of lymphoproliferation and immunosuppression when injected into adult C57BL/6 mice. The ecotropic/MCF (mink cell focus-inducing) mixture of MuLV stimulates polyclonal B lymphocyte proliferation and differentiation to antibody-secreting cells. Serum Ig levels are elevated(More)