The B-oligomer of pertussis toxin inhibits human immunodeficiency virus type 1 replication at multiple stages.
We have recently demonstrated that the binding subunit (B-oligomer) of pertussis toxin (PTX-B) deactivates CCR5 and inhibits entry of R5 human immunodeficiency virus type 1 (HIV-1) strains in activated primary T lymphocytes (M. Alfano et al., J. Exp. Med. 190:597-605, 1999). We now present evidence that PTX-B also affects a post-entry step of HIV-1 replication. While PTX-B inhibited fusion induced by R5 but not that induced by X4 envelopes, it blocked infection of T cells with recombinant HIV-1 particles pseudotyped with R5, X4, and even murine leukemia virus or vesicular stomatitis virus envelopes. It also suppressed HIV-1 RNA synthesis in cultures of infected peripheral blood mononuclear cells when new infections had been inhibited by zidovudine, and it reduced Tat-dependent expression of the luciferase reporter gene controlled by the HIV-1 long terminal repeat (LTR). Surprisingly, PTX-B did not affect expression from the cytomegalovirus promoter, nor did it reduce the basal (Tat-independent) expression from the LTR promoter. These results indicate that PTX-B inhibits HIV-1 infection at both the entry and the post-entry stages of viral replication, with the post-entry activity specifically affecting transcription or stability of Tat-stimulated HIV-1 mRNAs.
Alfano
M
M
The Picower Institute for Medical Research, Manhasset, New York 11030, USA.
Pushkarsky
T
T
Poli
G
G
Bukrinsky
M
M
D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000235:genetics; D015696:Gene Products, tat / Q000235:genetics; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D009052:Leukemia Virus, Murine / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000821:virology; D008561:Membrane Fusion / Q000187:drug effects*; D037342:Pertussis Toxin; D011108:Polymers; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000821:virology; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000737:chemistry / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D011108:Polymers; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; D010566:Virulence Factors, Bordetella; D054322:tat Gene Products, Human Immunodeficiency Virus; D037342:Pertussis Toxin