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Construction of a High Titer Infectious HIV-1 Subtype C Proviral Clone from South Africa
Institut für Virologie und Immunbiologie, Universität Würzburg, Versbacher Straße 7, 97078 Würzburg, Germany
Division of Medical Virology, Faculty of Medicine & Health Sciences, Stellenbosch University/National Health Laboratory Service, Tygerberg, 7505, Cape Town, South Africa
Present address: Division of Medical Virology, Faculty of Medicine & Health Sciences, Stellenbosch University/National Health Laboratory Service, Tygerberg, 7505, Cape Town, South Africa
* Author to whom correspondence should be addressed.
Received: 26 July 2012; in revised form: 13 September 2012 / Accepted: 13 September 2012 / Published: 24 September 2012
Abstract: The Human Immunodeficiency Virus type 1 (HIV-1) subtype C is currently the predominant subtype worldwide. Cell culture studies of Sub-Saharan African subtype C proviral plasmids are hampered by the low replication capacity of the resulting viruses, although viral loads in subtype C infected patients are as high as those from patients with subtype B. Here, we describe the sequencing and construction of a new HIV-1 subtype C proviral clone (pZAC), replicating more than one order of magnitude better than the previous subtype C plasmids. We identify the env-region for being the determinant for the higher viral titers and the pZAC Env to be M-tropic. This higher replication capacity does not lead to a higher cytotoxicity compared to previously described subtype C viruses. In addition, the pZAC Vpu is also shown to be able to down-regulate CD4, but fails to fully counteract CD317.
Keywords: HIV-1; subtype C; proviral plasmid; viral replication; resistance assays; Vpu; CD317; CD4
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Jacobs, G.B.; Bock, S.; Schuch, A.; Moschall, R.; Schrom, E.-M.; Zahn, J.; Reuter, C.; Preiser, W.; Rethwilm, A.; Engelbrecht, S.; Kerkau, T.; Bodem, J. Construction of a High Titer Infectious HIV-1 Subtype C Proviral Clone from South Africa. Viruses 2012, 4, 1830-1843.
Jacobs GB, Bock S, Schuch A, Moschall R, Schrom E-M, Zahn J, Reuter C, Preiser W, Rethwilm A, Engelbrecht S, Kerkau T, Bodem J. Construction of a High Titer Infectious HIV-1 Subtype C Proviral Clone from South Africa. Viruses. 2012; 4(9):1830-1843.
Jacobs, Graeme B.; Bock, Stefanie; Schuch, Anita; Moschall, Rebecca; Schrom, Eva-Maria; Zahn, Juliane; Reuter, Christian; Preiser, Wolfgang; Rethwilm, Axel; Engelbrecht, Susan; Kerkau, Thomas; Bodem, Jochen. 2012. "Construction of a High Titer Infectious HIV-1 Subtype C Proviral Clone from South Africa." Viruses 4, no. 9: 1830-1843.