title: Coreceptor utilization of HIV type 1 subtype E viral isolates from Thai men with HIV type 1-infected and uninfected wives.
abstract: 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.
authors.affiliation: HIV Immunology and Diagnostics Branch, DASTLR, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Utaiwan
authors.initials: U
authors.lastname: Utaipat
authors.forename: Ann
authors.initials: A
authors.lastname: Duerr
authors.forename: Donna L
authors.initials: DL
authors.lastname: Rudolph
authors.forename: Chunfu
authors.initials: C
authors.lastname: Yang
authors.forename: Salvatore T
authors.initials: ST
authors.lastname: Butera
authors.forename: Davis
authors.initials: D
authors.lastname: Lupo
authors.forename: Tracy
authors.initials: T
authors.lastname: Pisell
authors.forename: Arunrat
authors.initials: A
authors.lastname: Tangmunkongvorakul
authors.forename: Nuonchuen
authors.initials: N
authors.lastname: Kamtorn
authors.forename: Niwes
authors.initials: N
authors.lastname: Nantachit
authors.forename: Tippavan
authors.initials: T
authors.lastname: Nagachinta
authors.forename: Vinai
authors.initials: V
authors.lastname: Suriyanon
authors.forename: Valerie
authors.initials: V
authors.lastname: Robison
authors.forename: Kenrad E
authors.initials: KE
authors.lastname: Nelson
authors.forename: Nopporn
authors.initials: N
authors.lastname: Sittisombut
authors.forename: Renu B
authors.initials: RB
authors.lastname: Lal
mesh_terms: 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
chemical_list: 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