Clade-specific differences in active viral replication and compartmentalization.
OBJECTIVE
This review focuses on the impact of HIV-1 clade-specific polymorphisms on the dynamics of viral replication and compartmentalization in vivo.


RESULTS
HIV-1 transcription and compartmentalization are essentially modulated by interconnected parameters: cellular activation by T-cell receptor engagement or cytokine signalling in different tissues, and viral polymorphisms in the long terminal repeat and Tat protein. Moreover, the gut-associated lymphoid tissue plays a central role in HIV-1 pathogenesis. It selectively supports viral replication in primary infection and may influence viral quasispeciation during interleukin-7 treatment. In addition, interleukin-7, permanently released by the intestinal epithelial cells, preferentially activates the HIV-1 clade C promoter versus the B and E counterparts.


CONCLUSIONS
In view of the influence of long terminal repeat polymorphisms on the replication of different clades and the importance of HIV-1 replication in the gut-associated lymphoid tissue during primary infection, it will be important to show whether the amplitude and speed of gut-associated lymphoid tissue depletion in primary infection are also clade dependent and can impact disease progression. In the context of therapeutic interleukin-7 treatment, this cytokine might well foster growth of HIV-1 clade C and perhaps clade A viruses. This needs attention.
Unité de Rétrovirologie Moléculaire, Department of Virology, Institut Pasteur, 75015 Paris, France. joo@pasteur.fr
Monica
M
Sala
Mireille
M
Centlivre
Simon
S
Wain-Hobson