Laboratory of Infectious Diseases

Peter L. Collins, Ph.D.

Chief, RNA Viruses Section

Dr. Collins received a Ph.D. in 1981 from the University of Connecticut. He conducted postdoctoral research at the University of North Carolina from 1981 to 1984. At that time, he joined the Laboratory of Infectious Diseases, where he received tenure in 1990. He serves on the editorial boards of the Journal of Virology, Virology, and Virus Research.

Dr. Collins’ laboratory works with paramyxoviruses, which are enveloped, cytoplasmic viruses with single-stranded negative-sense RNA genomes of 13-19 kb. Paramyxoviruses include a number of well-established, important pathogens of humans (e.g., mumps and measles viruses) and animals (e.g., rinderpest and Newcastle disease viruses), and also include emerging pathogens (e.g., Nipah and Hendra viruses). Dr. Collins played a pioneering role in sequencing and characterizing the genomes and encoded gene products of several paramyxoviruses, in particular human respiratory syncytial virus (RSV). Later, he played an important role in developing reverse genetics systems for this type of virus, whereby complete infectious virus can be recovered from transfected cDNAs. This provides the basis for introducing predetermined changes into infectious virus.

RSV is a leading worldwide agent of respiratory tract disease, especially in young infants. The laboratory also studies several other major pediatric respiratory pathogens, namely human parainfluenza virus serotypes 1, 2, and 3 (HPIV1, 2, and 3) and human metapneumovirus (HMPV). Other areas of interest include the avian paramyxoviruses (APMV), represented by Newcastle disease virus (NDV), and pneumonia virus of mice (PVM), a murine relative of RSV.

The laboratory is presently using reverse genetics to design live, attenuated vaccines for RSV, HPIV1-3, and HMPV for intranasal administration to infants as a universal pediatric vaccine. In studies supported in part by collaboration with industry, lead candidates for RSV and HPIV3 vaccines are in Phase I and II clinical trials. The laboratory also is using NDV and other APMV as vaccine vectors to express protective antigens of emerging pathogens. The laboratory also investigates basic features of viral molecular biology, pathogenesis, and immunobiology that provide an intellectual foundation for the translational vaccine studies.

Major Areas of Research

• Studies in molecular biology, immunobiology, and pathogenesis of the human respiratory pathogens RSV, HPIV1-3, and HMPV: Studies involve infection in vitro of epithelial cells, macrophages, and other cell types and in vivo infection of experimental animals to elucidate the viral replicative cycle, interactions between viral and host components, the host response to infection, and mechanisms of pathogenesis. Studies include mini-replicons, complete recombinant virus, and engineered viral variants with gene knock-outs or mutated proteins.
• Development of novel attenuating mutations that are introduced by reverse genetics into RSV, HPIV1-3, and HMPV to produce live, attenuated “designer” vaccine candidates. Candidates are evaluated preclinically in monolayer cell cultures, in vitro models of airway epithelium, rodents, and nonhuman primates.
• Evaluation of candidate live vaccines in clinical studies with clinical collaborators, as well as wild type viruses in adult volunteers
• Studies with wild type and “designer” mutants of PVM in mice to characterize viral infection and host responses to an RSV-like virus in a convenient permissive host
• Development of vaccine vectors based on HPIV and APMV such as NDV for use against highly pathogenic emerging viruses exemplified by SARS coronavirus, avian influenza, and Ebola viruses

Selected Publications

View list in PubMed.

Samuel AS, Paldurai A, Kumar S, Collins PL, Samal SK. The complete genome sequence for avian paramyxovirus (APMV) serotype 5 strain Kunitachi completes the analysis of the nine APMV serotypes and reveals the longest APMV genome. PLoS One. In press.

Bukreyev AA, Dinapoli JM, Yang L, Murphy BR, Collins PL. Mucosal parainfluenza virus-vectored vaccine against Ebola virus replicates in the respiratory tract of vector-immune monkeys and is immunogenic. Virology. 2010 Apr 10;399(2):290-8.

Le Nouen C, Munir S, Losq S, Winter CC, McCarty T, Stephany DA, Holmes KL, Bukreyev A, Rabin RL, Collins PL, Buchholz UJ. Infection and maturation of monocyte-derived human dendritic cells by human respiratory syncytial virus, human metapneumovirus, and human parainfluenza virus type 3. Virology. 2009 Mar 1;385(1):169-82.

Buchholz UJ, Ward JM, Lamirande EW, Heinze B, Krempl CD, Collins PL. Deletion of nonstructural proteins NS1 and NS2 from pneumonia virus of mice attenuates viral replication and reduces pulmonary cytokine expression and virulence. J Virol. 2009 Feb;83(4):1969-80.

Bukreyev A, Yang L, Fricke J, Cheng L, Ward JM, Murphy BR, Collins PL. The secreted form of respiratory syncytial virus G glycoprotein helps the virus evade antibody-mediated restriction of replication by acting as an antigen decoy and through effects on Fc receptor-bearing leukocytes. J Virol. 2008 Dec;82 (24):12191-204.

Collins PL, Graham BS. Viral and host factors in human respiratory syncytial virus pathogenesis. J Virol. 2008 Mar;82(5):2040-55.

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