Stringent requirement for the C protein of wild-type measles virus for growth both in vitro and in macaques.
The P gene of measles virus (MV) encodes the P protein and three accessory proteins (C, V, and R). However, the role of these accessory proteins in the natural course of MV infection remains unclear. For this study, we generated a recombinant wild-type MV lacking the C protein, called wtMV(C-), by using a reverse genetics system (M. Takeda, K. Takeuchi, N. Miyajima, F. Kobune, Y. Ami, N. Nagata, Y. Suzaki, Y. Nagai, and M. Tashiro, J. Virol. 74:6643-6647). When 293 cells expressing the MV receptor SLAM (293/hSLAM) were infected with wtMV(C-) or parental wild-type MV (wtMV), the growth of wtMV(C-) was restricted, particularly during late stages. Enhanced green fluorescent protein-expressing wtMV(C-) consistently induced late-stage cell rounding and cell death in the presence of a fusion-inhibiting peptide, suggesting that the C protein can prevent cell death and is required for long-term MV infection. Neutralizing antibodies against alpha/beta interferon did not restore the growth restriction of wtMV(C-) in 293/hSLAM cells. When cynomolgus monkeys were infected with wtMV(C-) or wtMV, the number of MV-infected cells in the thymus was >1,000-fold smaller for wtMV(C-) than for wtMV. Immunohistochemical analyses showed strong expression of an MV antigen in the spleen, lymph nodes, tonsils, and larynx of a cynomolgus monkey infected with wtMV but dramatically reduced expression in the same tissues in a cynomolgus monkey infected with wtMV(C-). These data indicate that the MV C protein is necessary for efficient MV replication both in vitro and in cynomolgus monkeys.
Takeuchi
Kaoru
K
Department of Infection Biology, Graduate School of Comprehensive Human Sciences and Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. ktakeuch@md.tsukuba.ac.jp
Takeda
Makoto
M
Miyajima
Naoko
N
Ami
Yasushi
Y
Nagata
Noriyo
N
Suzaki
Yuriko
Y
Shahnewaz
Jamila
J
Kadota
Shin-Ichi
S
Nagata
Kyosuke
K
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002522:Chlorocebus aethiops; D015967:Gene Expression Regulation, Viral; D008252:Macaca fascicularis; D008457:Measles / Q000821:virology; D008459:Measles virus / Q000235:genetics / Q000254:growth & development*; D008969:Molecular Sequence Data; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
D017361:Viral Nonstructural Proteins