Plasmodium UIS3 avoids host cell-autonomous exclusion that requires GABARAPs but not LC3 and autophagy

• Published in: Parasitology international 2021-08, Vol.83, p.102335-102335, Article 102335
• Main Authors: Pradipta, Ariel, Bando, Hironori, Ma, Ji Su, Tanaka, Shun, Sasai, Miwa, Yamamoto, Masahiro
• Format: Article
• Language: English
• Subjects: Atg proteins; Autophagy; GABARAPs; LC3s; Plasmodium berghei; Upregulated in infective sporozoites 3 (UIS3)
• ISSN: 1383-5769; 1873-0329
• DOI: 10.1016/j.parint.2021.102335

Sporozoites of the etiological agent of malaria, Plasmodium, form parasitophorous vacuoles (PVs) in hepatocytes. The PV membranes (PVM) are coated with a well-known host autophagy marker LC3 and parasite-derived protein called Upregulated in infective sporozoites 3 (UIS3), which has been shown to interact with LC3 and inhibit LC3-mediated autophagic disruption at the PV. Although uis3(−) sporozoites cannot proliferate in wild-type cells, they can replicate efficiently in cells defective in autophagy due to the lack of Atg proteins such as Atg3, Atg5 and Atg7, since these Atg proteins are essential for processing of LC3. However, it remains to be seen whether other Atg proteins participate in the restriction of uis3(−) parasite growth. Here we show that, despite essential roles of Atg9 and Atg14 in autophagy, both proteins are dispensable for the restriction of uis3(−) parasite growth. Moreover, we found that cells lacking LC3 proteins are also able to restrict uis3(−) parasite growth. In sharp contrast, GABARAPs, another subfamily of mammalian Atg8, participated in suppression of uis3(−) parasite growth. Taken together, contrary to a previous model in which UIS3 avoids host LC3- and autophagy-dependent parasite elimination program, our data demonstrate a role of GABARAPs for suppression of uis3(−) parasite growth in a manner independent on autophagy. [Display omitted] •Plasmodium berghei sporozoites lacking UIS3 can proliferate in cells lacking Atg3, Atg5 or Atg7 but not in wild-type cells.•Autophagy defective cells such as Atg9 or Atg14-deficient cells restrict uis3(−) parasite growth.•GABARAPs but not LC3s are important for the restriction of uis3(−) parasite growth.