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J Howlett

Publications and source records attributed to J Howlett.

24 records · Page 2Linked to original sources

Reversion of the attenuated and temperature-sensitive phenotypes of the Sabin type 3 strain of poliovirus in vaccinees.

Isolates of type 3 poliovirus from vaccine-recipients were characterized in terms of virulence, sensitivity of growth to high temperatures, and differences in genome structure from the Sabin type 3 vaccine strain. These included point mutations in the region of the genome coding for the structural proteins and in the 5' noncoding region, and the presence of type 1 or type 2 poliovirus genomic sequences resulting from intertypic recombination. Isolates from healthy vaccinees resembled those from vaccine-associated cases of poliomyelitis in all of these properties. Suppression of the temperature-sensitive phenotype was strictly correlated with reversion to virulence in nonrecombinant type 3 strains. Recombinant isolates were more attenuated than expected, even when they had lost all mutations known to attenuate the type 3 vaccine strain.

Base Sequence↗

The temperature sensitivity of the Sabin type 3 vaccine strain of poliovirus: molecular and structural effects of a mutation in the capsid protein VP3.

The growth of the Sabin strain of type 3 poliovirus is reduced at high temperatures compared to that of its virulent precursor strain Leon. Recombinant viruses have been generated from infectious cDNA clones and demonstrate that the temperature-sensitive (ts) phenotype is mainly attributable to a difference in residue 91 of the virion protein VP3. Examination of non-ts mutants derived in vitro or in vivo reveals the existence of second site mutations some of which are clearly able to suppress the ts phenotype. The location of residue 91 of VP3, and of a number of candidate suppressor mutations, in the atomic structure of the virion suggests that the ts phenotype may result in destabilization of the particle and that the suppressors may function by stabilizing specific interfaces. It is not yet clear whether the ts phenotype is expressed at the level of the particle or in the form of defects in assembly or uncoating of the virion, or all three.

Amino Acid Sequence↗

An organ culture model for examining epidermal desquamation.

The use of organ cultures of mouse ear skin for examining mechanisms of stratum corneum shedding has been investigated. The formation and loss of stratum corneum cells was assessed by electron microscopic autoradiography and from counts of stratum corneum cell layers taken from sections of plastic-embedded specimens. Using media supplemented with cortisone, there was a linear accumulation of stratum corneum cell layers and the rate of epidermal cell formation corresponded approximately to that in vivo. Cells that accumulated at the stratum corneum surface were loose and could consistently be removed by treatment with detergent and ultrasonication indicating the persistence of shedding mechanisms in vitro.

Animals↗