Mutant murine leukemia virus Gag proteins lacking proline at the N-terminus of the capsid domain block infectivity in virions containing wild-type Gag.
We have investigated the properties of murine leukemia virus Gag mutants in which the p12-CA cleavage site is altered. In one mutant, the cleavage is blocked; in the other, the conserved proline at the N-terminus of CA has been replaced with glycine. No infectivity was detected in either mutant. Mutant particles cannot synthesize full-length DNA upon infecting permissive cells. Particles composed of a mixture of wild-type and mutant proteins have severely impaired infectivity. These mixed particles are defective in their ability to synthesize DNA upon infection, but this defect is less severe than the loss of infectivity. Thus, proteins lacking the correct N-terminus of CA inhibit DNA synthesis and also interfere with formation or integration of a full-length, normal provirus. The results imply that CA proteins function as part of a large, highly organized structure in reverse transcription and apparently at a later step as well.
Rulli
S J
SJ
HIV Drug Resistance Program, SAIC Frederick, National Cancer Institute-Frederick, P.O. Box B, Frederick, MD 21702-1201, USA.
Muriaux
D
D
Nagashima
K
K
Mirro
J
J
Oshima
M
M
Baumann
J G
JG
Rein
A
A
D000818:Animals; D036022:Capsid Proteins / Q000235:genetics / Q000502:physiology / Q000627:therapeutic use; D002460:Cell Line; D004270:DNA, Circular / Q000096:biosynthesis; D004279:DNA, Viral / Q000096:biosynthesis; D015683:Gene Products, gag / Q000235:genetics / Q000502:physiology / Q000627:therapeutic use*; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D007942:Leukemia, Experimental / Q000517:prevention & control*; D008854:Microscopy, Electron; D009154:Mutation; D011392:Proline / Q000172:deficiency*; D012367:RNA, Viral / Q000378:metabolism; D012192:Retroviridae Infections / Q000517:prevention & control*; D014412:Tumor Virus Infections / Q000517:prevention & control*; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology; D014771:Virion / Q000502:physiology / Q000648:ultrastructure
D036022:Capsid Proteins; D004270:DNA, Circular; D004279:DNA, Viral; D015683:Gene Products, gag; D012367:RNA, Viral; D014764:Viral Proteins; D011392:Proline