Requirement of the human T-cell leukemia virus p12 and p30 products for infectivity of human dendritic cells and macaques but not rabbits.
The identification of the genes necessary for human T-cell leukemia virus (HTLV-1) persistence in humans may provide targets for therapeutic approaches. We demonstrate that ablation of the HTLV-1 genes encoding p12, p30, or the HBZ protein, does not affect viral infectivity in rabbits and in this species, only the absence of HBZ is associated with a consistent reduction in virus levels. We observed reversion of the HTLV-1 mutants to the HTLV-1 wild-type genotype in none of the inoculated rabbits. In contrast, in macaques, the absence of HBZ was associated with reversion of the mutant virus to the wild-type genotype in 3 of the 4 animals within weeks from infection. Similarly, reversion to the wild type was observed in 2 of the 4 macaque inoculated with the p30 mutant. The 4 macaques exposed to the p12 knock remained seronegative, and only 2 animals were positive at a single time point for viral DNA in tissues. Interestingly, we found that the p12 and the p30 mutants were also severely impaired in their ability to replicate in human dendritic cells. These data suggest that infection of dendritic cells may be required for the establishment and maintenance of HTLV-1 infection in primate species.
Valeri
Valerio W
VW
Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD 20892-5065, USA.
Hryniewicz
Anna
A
Andresen
Vibeke
V
Jones
Kathy
K
Fenizia
Claudio
C
Bialuk
Izabela
I
Chung
Hye Kyung
HK
Fukumoto
Risaku
R
Parks
Robyn Washington
RW
Ferrari
Maria Grazia
MG
Nicot
Christophe
C
Cecchinato
Valentina
V
Ruscetti
Frank
F
Franchini
Genoveffa
G
D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D005260:Female; D017353:Gene Deletion; D005814:Genes, Viral; D016355:Genes, pX; D005838:Genotype; D015490:HTLV-I Infections / Q000276:immunology / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008253:Macaca mulatta; D016296:Mutagenesis; D009154:Mutation; D011817:Rabbits; D012191:Retroviridae Proteins / Q000235:genetics* / Q000502:physiology*; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics* / Q000502:physiology*; D014774:Virulence / Q000235:genetics / Q000502:physiology
D050976:Basic-Leucine Zipper Transcription Factors; D017931:DNA Primers; D004279:DNA, Viral; C479751:HBZ protein, human T-cell leukemia virus type I; D012191:Retroviridae Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C084305:p12I protein, Human T-lymphotropic virus 1; C072814:tof protein, Human T-lymphotropic virus 1