TABLE 5.

Temperature sensitivity and attenuation phenotype of rHPIV1 L protein codon-992 substitution mutants

VirusNo. of nucleotide changes needed to restore wild-type amino acidVirus titer at 32°C (log10 TCID50/ml)bMean log10 reductiona in virus titer at indicated temp (°C)Replication of virus in hamsters
No. of animalsMean titer of virus (log10 TCID50/g ± SE)
3536373839Nasal turbinatesLungs
rHPIV1-wild type07.50.10.10.50.61.2304.2 ± 0.23.9 ± 0.4
rHPIV1 L992Fcp4518.10.20.31.30.92.4124.4 ± 0.33.0 ± 0.2
rHPIV1 L992M18.40.20.20.40.72.764.7 ± 0.33.2 ± 0.4
rHPIV1 L992I18.20.30.50.52.74.3b64.1 ± 0.22.6 ± 0.3
rHPIV1 L992W18.50.00.50.83.73.864.0 ± 0.23.3 ± 0.1
rHPIV1 L992H18.10.31.31.31.84.963.3 ± 0.23.4 ± 0.1
rHPIV1 L992V16.20.70.51.52.54.06<1.5 ± 0.0c1.7 ± 0.2
rHPIV1 L992N27.80.60.30.62.03.362.7 ± 0.2<1.5 ± 0.0
rHPIV1 L992Y28.50.00.20.51.42.964.5 ± 0.23.3 ± 0.4
rHPIV1 L992K28.60.01.20.21.83.064.1 ± 0.33.1 ± 0.4
rHPIV1 L992A27.90.50.31.23.04.563.6 ± 0.23.2 ± 0.3
rHPIV1 L992C27.30.72.22.94.0>4.963.2 ± 0.21.7 ± 0.1
  • a Mean reduction in titer compared to titer at 32°C. Each value represents the average of two or three experiments.

  • b A mutant is considered to be temperature sensitive if its reduction in titer at a nonpermissive temperature is 100-fold greater than the reduction of titer of the wild-type HPIV1 tested at that temperature (indicated by values in bold).

  • c Underlined values represent greater-than-100-fold reduction compared to that for rHPIV1 in the same pulmonary compartment.