Chronic HIV-1 Infection Frequently Fails to Protect against Superinfection

Abstract

Reports of HIV-1 superinfection (re-infection) have demonstrated that the immune response generated against one strain of HIV-1 does not always protect against other strains. However, studies to determine the incidence of HIV-1 superinfection have yielded conflicting results. Furthermore, few studies have attempted to identify superinfection cases occurring more than a year after initial infection, a time when HIV-1-specific immune responses would be most likely to have developed. We screened a cohort of high-risk Kenyan women for HIV-1 superinfection by comparing partial gag and envelope sequences over a 5-y period beginning at primary infection. Among 36 individuals, we detected seven cases of superinfection, including cases in which both viruses belonged to the same HIV-1 subtype, subtype A. In five of these cases, the superinfecting strain was detected in only one of the two genome regions examined, suggesting that recombination frequently occurs following HIV-1 superinfection. In addition, we found that superinfection occurred throughout the course of the first infection: during acute infection in two cases, between 1–2 y after infection in three cases, and as late as 5 y after infection in two cases. Our results indicate that superinfection commonly occurs after the immune response against the initial infection has had time to develop and mature. Implications from HIV-1 superinfection cases, in which natural re-exposure leads to re-infection, will need to be considered in developing strategies for eliciting protective immunity to HIV-1.

IFN-α Induces APOBEC3G, F, and A in Immature Dendritic Cells and Limits HIV-1 Spread to CD4+ T Cells

“…HIV-1 envelop (env) V1-V5 gene region was amplified by performing high-fidelity nested PCR using an EasyA kit (Stratagene). The primers used were as follows: round 1 (product size 1415 bp), forward 59-TTGCAATAGAAAAATTCTCCTC-39, and reverse 59-CCTGGTGGGTGCTACTCCTA-39); round 2 (product size 1098 pb), forward 59-CCATGTGTAAAGTTAACCCC-39, and reverse, 59-ATGAGGGACAATTGAGAAGTGTCTAG-39; PCR condition as described in (27). Amplicons were purified by using a high pure PCR product purification kit (Roche), and cloned into the TA cloning vector provided in a TOPO TA cloning kit (Invitrogen) in accordance with the manufacturer's instructions.…”

Longitudinal Quasispecies Analysis of Viral Variants in HIV Type 1 Dually Infected Individuals Highlights the Importance of Sequence Identity in Viral Recombination

“…In a recent study by Piantadosi et al, of seven dually infected Kenyan women, only one individual was found to harbor a virus that was a recombinant of the parental viruses (subtypes A and D) in the V1V5 region of env. 3 This virus was found in the minority of sequences at 73 days postinfection but absent for the next 4.5 years until its reappearance as a 25% proportion of env sequences. 3 In a study by Gerdhart et al that analyzed the vpu=gp120 region of env sequences from specimens obtained at 3-month intervals from a subject triply infected by two strains of subtype A and a subtype C virus, exhibiting symptoms of late-stage disease, env analysis identified several URFs; however, these recombinants always comprised a small minority (<1%) of the viral quasispecies in the individual at each of the time points analyzed.…”

“…3 This virus was found in the minority of sequences at 73 days postinfection but absent for the next 4.5 years until its reappearance as a 25% proportion of env sequences. 3 In a study by Gerdhart et al that analyzed the vpu=gp120 region of env sequences from specimens obtained at 3-month intervals from a subject triply infected by two strains of subtype A and a subtype C virus, exhibiting symptoms of late-stage disease, env analysis identified several URFs; however, these recombinants always comprised a small minority (<1%) of the viral quasispecies in the individual at each of the time points analyzed. 11 To best examine the role of sequence identity in the generation of recombinants, individuals dually infected with concordant as well as discordant HIV-1 subtypes must be studied.…”

“…[1][2][3][4][5][6][7][8][9] Among such studies includes one published by Baird et al, which examined the C1C4 region of env for recombination between two discordant HIV-1 subtypes, A and D, in cell culture demonstrating an abundance of recombinants and revealing recombination breakpoints occurring more frequently in the constant than in the variable regions of the viral envelope. 8 Subsequent in vitro studies with these discordant strains also revealed that factors such as replicative fitness contribute to the frequency at which two viral strains recombine.…”

Dynamics of HIV Type 1 Recombination Following Superinfection

“…However, superinfection may be difficult to detect when the superinfecting virus is of the same subtype as the initial virus, and the detection of possible consequent recombinants is restricted to a handful of reports. [2][3][4][5][6] It has previously been reported that superinfection with a virus of different subtype can result in replacement of the original virus. 2,7-9 Fang et al 4 showed replacement of subtype A virus with AC, but did not show the presence of ''pure'' subtype C virus, so the superinfection could have been with an AC recombinant.…”