Construction of a high titer infectious HIV-1 subtype C proviral clone from South Africa

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 (2012-09-24)

CITATION: Jacobs, G. B. et al. 2012. Construction of a high titer infectious HIV-1 subtype C proviral clone from South Africa. Viruses, 4(9):1830-1843; doi:10.3390/v4091830.

The original publication is available at http://www.mdpi.com/journal/viruses

Article

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.

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