Document 0074
 DOCN  M9610074
 TI    The role of the cell cycle in HIV-1 infection.
 DT    9601
 AU    Zack JA; Department of Medicine, UCLA School of Medicine, USA.
 SO    Adv Exp Med Biol. 1995;374:27-31. Unique Identifier : AIDSLINE
       MED/96047235
 AB    Infection of quiescent lymphocytes with human immunodeficiency virus
       type 1 (HIV-1) does not result in production of progeny virus. We have
       previously reported that although HIV-1 can enter quiescent lymphocytes
       with high efficiency, the reverse transcription process does not go to
       completion. This results in a viral genome which is composed partly of
       viral RNA and partly of viral DNA. If a mitogenic signal is applied
       shortly after infection to a cell harboring such a structure, reverse
       transcription can go to completion and progeny virus will be produced.
       However, this partially reverse transcribed structure is extremely
       labile, and the efficiency of virus rescue decreases rapidly, with
       increasing times between infection and activation. Our laboratory is
       using inhibitors of cell activation to identify at which stage of the
       cell cycle this block to reverse transcription occurs. We have found
       that agents that arrest the cell in the late G1 phase of the cell cycle
       do not alter the ability of the virus to complete reverse transcription.
       However, agents that inhibit activation of the cell by blocking
       transition through G1 prevent completion of reverse transcription. It
       thus appears that immunosuppression of the target cell may be a means of
       preventing productive infection of the cell. We have also been using the
       severe combined immunodeficient mouse implanted with human tissue
       (SCID-hu) as an in vivo model to study HIV-1 pathogenic properties. When
       human fetal thymic implants in these animals are infected by HIV-1,
       profound depletion of CD4-bearing human thymocytes is seen.(ABSTRACT
       TRUNCATED AT 250 WORDS)
 DE    Acquired Immunodeficiency Syndrome/*PATHOLOGY  Animal  Cell Cycle/DRUG
       EFFECTS/*PHYSIOLOGY  Cell Differentiation/PHYSIOLOGY  Human  *HIV-1
       Mice  Support, U.S. Gov't, P.H.S.  Transcription, Genetic/DRUG EFFECTS
       *Virus Replication  JOURNAL ARTICLE  REVIEW  REVIEW, TUTORIAL

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