AEGiS-14IAC: Early post entry events in HIV-2 replication.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Early post entry events in HIV-2 replication.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. WeOrA1257)

McKnight A, Aubin KA, Dittmar MT, Marchant D, Reuter S, Schmitz C
UCL, London, United Kingdom

BACKGROUND: Certain human cell lines and primary macrophage cultures are restricted to infection by a primary isolate prCBL-23, of human immunodeficiency virus type 2 (HIV-2) but not a lab adapted variant CBL-23. Early steps of the viral life cycle of prCBL-23, such as fusion at the plasma membrane and reverse transcription are fully supported. Post-integration events, transcription, translation, assembly, budding, and maturation into infectious virions are also functional in restrictive cells. HIV-2 pseudotype particles with Vesicular Stomatitis Virus envelope G protein which delivers HIV into an endocytic compartment, overcomes the block to infection. We postulate that the preintegration complexes are trapped in a cellular compartment preventing further steps cycle that lead to integration of the provirus. We suggest that delivery into an appropriate cellular compartment is a critical step during the entry process of HIV.

METHODS: We used a PCR cloning technique to make molecular clones of prCBL-23 and CBL-23 and swapped between genomic regions in an attempt to find the genes responsible for the restriction. To test if the restricted and non-restricted viruses located to different cellular compartments after fusion with the plasma membrane we used cellular fractionation techniques to follow trafficking of the virus.

RESULTS: Swapping of the viral genomes localised the genes in CBL-23 that allowed it to overcome the restriction to infection. Furthermore, we demonstrated that the restricted and unrestricted viruses located to different cellular compartments in the restricted cell types.

CONCLUSIONS: Specific viral genes encoded within the HIV-2 genome enable it to reach an appropriate cellular compartment after fusion at the cell membrane. Localisation to this site is necessary for access to the nucleus at least in certain cell types.

Keywords: AEGIS, HIV-2, Virus Replication, HIV, Virion, Viral Envelope Proteins, Proviruses, HIV Infections, HIV Long Terminal Repeat, Membrane Glycoproteins, HIV Antigens, Transcription, Genetic, G protein, vesicular stomatitis virus, Human, Metabolism, virology, genetics, immunology

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WeOrA1257