Endocytosis constitute the infectious route of HIV-1 entry in human and rabbit monocytes lacking the CD4 receptor.
To obtain "functionally" CD4 negative human monocytes (0-5 CD4 +/1 x 10(6)/cells), 50 ng/5.10(5) cells of OKT4A were added daily after a pre-incubation with OKT4A (100 ng/5.10(5) cells. In our experimental conditions the blocking the CD4 receptor of human monocytes with OKT4A monoclonal antibody did not prevent HIV-1 infection, although the level of virus replication appeared lower than that in cultures without OKT4A. "Naturally"CD4 negative rabbit monocytes infected with HIV-1 also released a detectable level of virus after 12-15 up 28-30 days. In "naturally" CD4 negative rabbit monocytes and "functionally" CD4 negative human monocytes, the virus particles entering via phagocytosis are not infectious because multiple well defined virions were observed in phagocytic vacuoles and the envelopes of these particles did not appear to interact with the vacuolar membrane. The infectious particles were represented by endocytic vesicles containing only the core of HIV after fusion between the viral envelope and endocytic membrane. Fusion between the viral envelope and plasma membrane on the cellular surface was never observed, in spite of examining greater than 1000 virions bound the surface of human and rabbit macrophage monocytes. The absence of cytopathic effect in the rabbit and human CD4 negative monocytes infected with HIV-1, and conversely the presence of specific sequences of HIV in the genomic DNA may indicate that the macrophages-monocytes serve as an important reservoir for the persistence of HIV in infected hosts, similar to the other related Lentiviruses. Our virological data have also demonstrated that virus infection can be transmitted from rabbit and human infected monocytes to uninfected H9 cells. This preliminary study may offer important evidence for the development and testing of vaccines and compounds that inhibit HIV penetration of susceptible cells.
Filice
G
G
Department of Infectious Diseases, University of Pavia, Italy.
Cereda
P M
PM
Orsolini
P
P
Soldini
L
L
Razzini
E
E
Campisi
D
D
Gulminetti
R
R
D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D002478:Cells, Cultured; D004705:Endocytosis; D015683:Gene Products, gag / Q000032:analysis; D016655:HIV Core Protein p24; D015497:HIV-1 / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000382:microbiology / Q000648:ultrastructure; D008854:Microscopy, Electron; D009000:Monocytes / Q000276:immunology / Q000382:microbiology* / Q000648:ultrastructure; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D011817:Rabbits; D014617:Vacuoles / Q000382:microbiology / Q000648:ultrastructure; D014758:Viral Core Proteins / Q000032:analysis; D014779:Virus Replication
D015704:CD4 Antigens; D015683:Gene Products, gag; D016655:HIV Core Protein p24; D014758:Viral Core Proteins; D012194:RNA-Directed DNA Polymerase