Coreceptor utilization of HIV type 1 subtype E viral isolates from Thai men with HIV type 1-infected and uninfected wives.
HIV-1 coreceptors CCR5 and CXCR4 play an important role in viral entry and pathogenesis. To better understand the role of viral tropism in HIV-1 transmission, we examined the coreceptor utilization of viral isolates obtained from men enrolled in a study of heterosexual transmission in northern Thailand. Viral isolates were obtained from HIV-1-positive males who had either HIV-1-infected spouses (RM; n = 5) or HIV-1-uninfected spouses (HM; n = 10). Viral isolates from 1 of the 5 RM males and 2 of the 10 HM males were CCR5 tropic, whereas isolates from 3 RM males and 6 of the HM male isolates were CXCR4 tropic. Of the nine X4-tropic isolates, seven also used at least one of the following coreceptors: CCR8, CCR1, CCR2b, or CX3CR1, and none employed CCR5 as an additional coreceptor. More importantly, three isolates, RM-15, HM-13, and HM-16 (one from a transmitter and two from nontransmitter), did not infect GHOST4.cl.34 cells expressing any of the known coreceptors. Further analysis using MAGI-plaque assays, which allow visualization of infected cells, revealed that RM-15 had low numbers of infected cells in MAGI-R5 and MAGI-X4 cultures, whereas HM-13 and HM-16 had high levels of plaques in MAGI-X4 cultures. Replication kinetics using activated lymphocytes revealed that these three isolates replicated in CCR5(+/+) as well as CCR5(-/-) peripheral blood mononuclear cells, suggesting that these isolates did not have an absolute requirement of CCR5 for viral entry. All three isolates were sensitive to the X4-antagonistic compounds T-22 and AMD3100. Analysis of the C2V3 region did not reveal any significant structural differences between any of the Thai subtype E isolates. Thus, there was no association between the pattern of coreceptor usage and transmissibility among these subtype E HIV-1 isolates.
Utaipat
Utaiwan
U
HIV Immunology and Diagnostics Branch, DASTLR, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Duerr
Ann
A
Rudolph
Donna L
DL
Yang
Chunfu
C
Butera
Salvatore T
ST
Lupo
Davis
D
Pisell
Tracy
T
Tangmunkongvorakul
Arunrat
A
Kamtorn
Nuonchuen
N
Nantachit
Niwes
N
Nagachinta
Tippavan
T
Suriyanon
Vinai
V
Robison
Valerie
V
Nelson
Kenrad E
KE
Sittisombut
Nopporn
N
Lal
Renu B
RB
D000595:Amino Acid Sequence; D000073883:CX3C Chemokine Receptor 1; D018932:Chemokine CCL2 / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism; D016384:Consensus Sequence; D018562:Disease Transmission, Infectious; D015699:HIV Envelope Protein gp120 / Q000737:chemistry; D015658:HIV Infections / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000378:metabolism* / Q000472:pathogenicity; D020010:Heterosexuality; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D054389:Receptors, CCR1; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000378:metabolism; D054401:Receptors, CCR8; D019718:Receptors, CXCR4 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism; D015728:Receptors, HIV / Q000737:chemistry / Q000378:metabolism*; D013785:Thailand; D014779:Virus Replication
C515300:CCR1 protein, human; C515334:CCR2 protein, human; C103330:CCR8 protein, human; D000073883:CX3C Chemokine Receptor 1; D018932:Chemokine CCL2; D019742:Chemokines, CC; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D054389:Receptors, CCR1; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D054401:Receptors, CCR8; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D015728:Receptors, HIV