title: Clearly different mechanisms of enhancement of short-lived Nef-mediated viral infectivity between SIV and HIV-1.
abstract: BACKGROUND
  One of the major functions of Nef is in the enhancement of the infectivity of the human and simian immunodeficiency viruses (HIV and SIV, respectively). However, the detailed mechanism of the enhancement of viral infectivity by Nef remains unclear. Additionally, studies of mechanisms by which Nef enhances the infectivity of SIV are not as intensive as those of HIV-1.
  
  
  METHODS
  We generated short-lived Nef constructed by fusing Nef to a proteasome-mediated protein degradation sequence to characterize the Nef role in viral infectivity.
  
  
  RESULTS
  The apparent expression level of the short-lived Nef was found to be extremely lower than that of the wild-type Nef. Moreover, the expression level of the short-lived Nef increased with the treatment with a proteasome inhibitor. The infectivity of HIV-1 with the short-lived Nef was significantly lower than that with the wild-type Nef. On the other hand, the short-lived Nef enhanced the infectivity of SIVmac239, an ability observed to be interestingly equivalent to that of the wild-type Nef. The short-lived Nef was not detected in SIVmac239, but the wild-type Nef was, suggesting that the incorporation of Nef into SIVmac239 is not important for the enhancement of SIVmac239 infectivity.
  
  
  CONCLUSIONS
  Altogether, the findings suggest that the mechanisms of infectivity enhancement by Nef are different between HIV-1 and SIVmac239. Lastly, we propose the following hypothesis: even when the expression level of a protein is extremely low, the protein may still be sufficiently functional.
authors.affiliation: Department of Pharmaceutical Biochemistry, Faculty of Life Sciences, Kumamoto University, 5-1Oe-Honmachi, Chuo-ku, Kumamoto, 8620973, Japan. tetsukuroe@gmail.com.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Harada
authors.affiliation: Department of Pharmaceutical Biochemistry, Faculty of Life Sciences, Kumamoto University, 5-1Oe-Honmachi, Chuo-ku, Kumamoto, 8620973, Japan. tkmnnbtk@gpo.kumamoto-u.ac.jp.|Innovative Collaboration Organization, Kumamoto University, 2-39-1 Kurokami, Chuo-ku, Kumamoto, 8608555, Japan. tkmnnbtk@gpo.kumamoto-u.ac.jp.
authors.forename: Nobutoki
authors.initials: N
authors.lastname: Takamune
authors.affiliation: Department of Pharmaceutical Biochemistry, Faculty of Life Sciences, Kumamoto University, 5-1Oe-Honmachi, Chuo-ku, Kumamoto, 8620973, Japan. shoji@gpo.kumamoto-u.ac.jp.
authors.forename: Shozo
authors.initials: S
authors.lastname: Shoji
authors.affiliation: Department of Pharmaceutical Biochemistry, Faculty of Life Sciences, Kumamoto University, 5-1Oe-Honmachi, Chuo-ku, Kumamoto, 8620973, Japan. misumi@gpo.kumamoto-u.ac.jp.
authors.forename: Shogo
authors.initials: S
authors.lastname: Misumi
mesh_terms: D015497:HIV-1 / Q000254:growth & development / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D015302:Simian Immunodeficiency Virus / Q000254:growth & development / Q000472:pathogenicity / Q000502:physiology*; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*; D014774:Virulence; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: C429284:NEF protein, SIV; D054334:Viral Regulatory and Accessory Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus