Accumulation of unintegrated circular viral DNA in monocytes and growth-arrested T cells following infection with HIV-1.
Cytocidal retrovirus infection is characterized by rapid accumulation of unintegrated viral DNA forms. These are thought to be generated by multiple rounds of reinfection and have been suggested to play a central role in cytopathogenesis. Here we have reviewed the work done in this area with HIV-1, mostly using acutely and chronically infected T cell and monocytic cell lines and in some cases T cells blocked at S phase of the cell cycle by aphidicolin treatment. To these studies, we have compared our findings with HIV-1 infected primary peripheral blood monocyte-derived macrophages and untreated and growth-arrested MT-2 cells, two biologically disparate cell populations. Using 1- and 2-long terminal repeat (LTR) circular forms as indicators of unintegrated viral DNA, we found similar rapid accumulation in both untreated and growth-arrested MT-2 cells. In contrast, we found much lower levels in monocyte/macrophages. Our findings suggest that accumulation of unintegrated viral DNA does not require virus production and reinfection in growth-arrested T cells. The significantly lower levels found in monocyte/macrophages may reflect superinfection resistance, allowing the maintenance of a persistent infection.
Sonza
S
S
AIDS Pathogenesis Research Unit, National Centre for HIV Virology Research, Macfarlane Burnet Centre for Medical Research Melbourne, Australia.
Kiernan
R E
RE
Maerz
A L
AL
Deacon
N J
NJ
McPhee
D A
DA
Crowe
S M
SM
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001483:Base Sequence; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification*; D006801:Humans; D008969:Molecular Sequence Data; D009000:Monocytes / Q000737:chemistry / Q000378:metabolism* / Q000382:microbiology*; D013601:T-Lymphocytes / Q000737:chemistry / Q000378:metabolism* / Q000382:microbiology*
D004279:DNA, Viral