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.

Broad Human Immunodeficiency Virus (HIV)–Specific T Cell Responses to Conserved HIV Proteins in HIV‐Seronegative Women Highly Exposed to a Single HIV‐Infected Partner

“…Another explanation is that HW were exposed to defective or replication-incompetent viruses that generated less envelope, and therefore fewer processed antigens, for presentation to T cells. However, initial studies of viruses isolated from the HM and RM indicated that all viruses were equally capable of infecting PBMCs (Butera 2002, personal communication) and that all had similar coreceptor usage profiles [39,46]. Thus, there is no evidence that the transmitting viruses had abnormal phenotypes.…”

The CCR5 and CXCR4 Coreceptors Are Both Used by Human Immunodeficiency Virus Type 1 Primary Isolates from Subtype C

“…Whether the frequency of subtype C X4 viruses will increase over time or will remain relatively low compared to that of subtype B infections remains to be determined. An analogy can be made to the HIV-1 subtype E epidemic in Thailand; there, early isolates were mostly of the NSI phenotype, but as the epidemic progressed, SI viruses started to appear with ever-increasing frequency (13,30,48,49,57). Further studies on subtype C infection may reveal the same trend.…”

Coreceptor Tropism in Human Immunodeficiency Virus Type 1 Subtype D: High Prevalence of CXCR4 Tropism and Heterogeneous Composition of Viral Populations

“…Although some studies have found no difference in phenotype among different subtypes (10,47,56), others have reported a trend for an unequal distribution of SI versus non-syncytiuminducing (NSI) viruses among different subtypes (1,5,17,35,39,(49)(50)(51)(52)57). One study (5) found that subtype D and CRF01_AE viruses were predominantly CXCR4-using (SI), whereas subtype A and C viruses were predominantly CCR5-using (non-SI, NSI).…”