Interaction of a noncytopathic human immunodeficiency virus type 1 (HIV-1) with target cells: efficient virus entry followed by delayed expression of its RNA and protein.
Recently described noncytopathic human immunodeficiency viruses type-1 (HIV-1) form a new category within the HIV-1 family due to their unique biological properties and predominant occurrence in symptom-free individuals. To study the mechanism of noncytopathic HIV-1 infection, we compared the infectivity and life cycles of two closely related HIV-1 clones with noncytopathic (N1T-E) or cytopathic (N1T-A) properties. N1T-E virus exhibited slow kinetics of infection in T cells and monocytes. Slow infection was not due to defective virus entry, because N1T-E and N1T-A exhibited equally efficient virus-cell fusion activity and nucleocapsid internalization. Kinetic studies of N1T-E genome expression revealed low levels of viral RNA, structural proteins, and Tat protein during the first 7 days after virus entry. In contrast, cells infected with the same dose of cytopathic N1T-A virus began to express high levels of genomic RNA, structural proteins, and Tat protein within 48 hr of infection; the expression peaked on Day 5, followed by complete cell lysis. No delay in N1T-E replication, as compared to N1T-A, was observed after transfection of cloned N1T-E proviral DNA. N1T-E virus had intact Tat, Rev, and fusion functions and replicated well in chronically infected cells. These results suggest that delayed processing or expression of HIV-1 genome during the early phase of the virus replicative cycle is an important determinant in noncytopathic infection.
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Molecular Virology Laboratory, St. Luke's/Roosevelt Hospital Center, New York, New York.
Sakai
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Sinangil
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Golub
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Volsky
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DJ
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics; D004261:DNA Replication; D015870:Gene Expression; D005814:Genes, Viral; D015757:Genes, rev; D015756:Genes, tat; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D007700:Kinetics; D008561:Membrane Fusion; D012367:RNA, Viral / Q000096:biosynthesis*; D012091:Repetitive Sequences, Nucleic Acid; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D012367:RNA, Viral