Blood monocytes harbor HIV type 1 strains with diversified phenotypes including macrophage-specific CCR5 virus.
BACKGROUND
Recent studies have shown that blood monocytes harbor human immunodeficiency virus type 1 (HIV-1) variants that are genotypically distinguishable from those in CD4(+) T cells. However, the biological function of monocyte-derived HIV-1 remains unclear.


METHODS
Using pseudovirus assay, we analyzed the phenotype conferred by monocyte-derived HIV-1 envelopes from 8 patients.


RESULTS
All pseudoviruses carrying monocyte-derived HIV-1 envelopes used CCR5; however, their use of additional coreceptors delineated 4 phenotypes in which viruses used (1) CCR5 only, (2) CCR5 and CXCR4, (3) CCR3 and CCR5, or (4) multiple coreceptors, including CCR1, CCR3, GPR15, CCR5, and CXCR4. More importantly, we observed 2 distinct cell tropism phenotypes for pseudoviruses carrying monocyte-derived envelopes: (1) monocyte-derived, macrophage-specific R5 (MDMS-R5) virus that, using CCR5 only, could infect monocyte-derived macrophages (MDMs) but not CD4(+) T cells and (2) dual tropic virus that infected both MDMs and primary CD4(+) T cells. We found blood monocytes harboring viruses with multiple phenotypes as early as 25 days before seroconversion and as late as 9 years after seroconversion.


CONCLUSIONS
These data suggest that HIV-1 circulating in blood monocytes represents diverse HIV-1 with multiple phenotypes and that MDMS-R5 viruses may play an important role in infection with and persistence of HIV-1 within the monocyte/macrophage lineage.
Xu
Younong
Y
Department of Laboratory Medicine, University of Washington School of Medicine, Seattle, Washington 98195-8070, USA.
Zhu
Haiying
H
Wilcox
Carrie K
CK
van't Wout
Angélique
A
Andrus
Thomas
T
Llewellyn
Nicholas
N
Stamatatos
Leonidas
L
Mullins
James I
JI
Corey
Lawrence
L
Zhu
Tuofu
T
D000328:Adult; D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics; D015658:HIV Infections; D015497:HIV-1 / Q000145:classification* / Q000302:isolation & purification / Q000378:metabolism / Q000472:pathogenicity; D006801:Humans; D008264:Macrophages / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000821:virology*; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics; D010641:Phenotype; D019713:Receptors, CCR5 / Q000378:metabolism*; D016415:Sequence Alignment
D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D019713:Receptors, CCR5