Human parainfluenza virus type 1 regulates cholesterol biosynthesis and establishes quiescent infection in human airway cells.

Human parainfluenza virus type 1 (hPIV1) and 3 (hPIV3) cause seasonal epidemics, but little is known about their interaction with human airway cells. In this study, we determined cytopathology, replication, and progeny virion release from human airway cells during long-term infection in vitro. Both viruses readily established persistent infection without causing significant cytopathic effects.

Cholesterol is required for stability and infectivity of influenza A and respiratory syncytial viruses.

Cholesterol-rich lipid raft microdomains in the plasma membrane are considered to play a major role in the enveloped virus lifecycle. However, the functional role of cholesterol in assembly, infectivity and stability of respiratory RNA viruses is not fully understood. We previously reported that depletion of cellular cholesterol by cholesterol-reducing agents decreased production of human parainfluenza virus type 1 (hPIV1) particles by inhibiting virus assembly.

Rescue of Sendai Virus from Cloned cDNA.

Sendai virus (SeV) is a non-segment negative-sense RNA virus that naturally infects and causes pneumonia in mice. As a prototypic member of the family Paramyxoviridae, SeV has been characterized well, and these studies revealed numerous traits of paramyxovirus biology. The reverse genetics system to rescue SeV was first established in 1995.

Cholesterol reducing agents inhibit assembly of type I parainfluenza viruses.

Many enveloped RNA viruses utilize lipid rafts for the assembly of progeny virions, but the role of cholesterol, a major component of rafts, on paramyxovirus budding and virion formation is controversial. In this study, we analyzed the effects of FDA-approved cholesterol-reducing agents, gemfibrozil and lovastatin, on raft formation and assembly of human parainfluenza virus type 1 (hPIV1) and Sendai virus (SeV). Treatment of the human airway epithelial A549 cells with the agents, especially when combined, significantly decreased production of infectious hPIV1 and SeV.

Critical role of Rab11a-mediated recycling endosomes in the assembly of type I parainfluenza viruses.

Paramyxoviruses replicate in the cytoplasm of infected cells and newly synthesized viral nucleocapsids (vRNPs) are transported to the plasma membrane to be incorporated into progeny virions. In this study, we analyzed the impact of the Rab11-mediated recycling pathway in Sendai virus (SeV) and human parainfluenza virus type 1 (hPIV1) vRNP transport. We found that suppression of Rab11 expression caused vRNP aggregation in the cytoplasm and reduced progeny virion formation.

First-in-human evaluation of a hexon chimeric adenovirus vector expressing HIV-1 Env (IPCAVD 002).

Background: We report the first-in-human safety and immunogenicity assessment of a prototype hexon chimeric adenovirus (Ad) serotype 5 (Ad5) vector containing the hexon hypervariable regions of Ad serotype 48 (Ad48) and expressing human immunodeficiency virus (HIV) type 1 EnvA.

Methods: Forty-eight Ad5 and Ad48 seronegative, HIV-uninfected subjects were enrolled in a randomized, double-blind, placebo-controlled, dose escalation phase 1 study. Four groups of 12 subjects received 10(9) to 10(11) viral particles (vp) of the Ad5HVR48.

Safety and immunogenicity of modified vaccinia Ankara in hematopoietic stem cell transplant recipients: a randomized, controlled trial.

Background: Modified vaccinia Ankara (MVA-BN, IMVAMUNE) is emerging as a primary immunogen and as a delivery system to treat or prevent a wide range of diseases. Defining the safety and immunogenicity of MVA-BN in key populations is therefore important.

Methods: We performed a dose-escalation study of MVA-BN administered subcutaneously in 2 doses, one on day 0 and another on day 28.

Evolution of an HIV glycan-dependent broadly neutralizing antibody epitope through immune escape.

Neutralizing antibodies are likely to play a crucial part in a preventative HIV-1 vaccine. Although efforts to elicit broadly cross-neutralizing (BCN) antibodies by vaccination have been unsuccessful, a minority of individuals naturally develop these antibodies after many years of infection. How such antibodies arise, and the role of viral evolution in shaping these responses, is unknown.