Analysis of infectious virus clones from two HIV1 superinfection cases suggests that the primary strains have lower fitness (original) (raw)
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HIV-1 sequence evolution in vivo after superinfection with three viral strains
Retrovirology, 2007
With millions of people infected worldwide, the evolution of HIV-1 in vivo has been the subject of much research. Although recombinant viruses were detected early in the epidemic, evidence that HIV-1 dual infections really occurred came much later. Dual infected patients, consisting of coinfected (second infection before seroconversion) and superinfected (second infection after seroconversion) individuals, opened up a new area of HIV-1 evolution studies. Here, we describe the in-depth analysis of HIV-1 over time in a patient twice superinfected with HIV-1, first with a subtype B (B2) strain and then with CRF01_AE after initial infection with a subtype B (B1) strain. The nucleotide evolution of gag and env-V3 of the three strains followed a similar pattern: a very low substitution rate in the first 2-3 years of infection, with an increase in synonymous substitutions thereafter. Convergent evolution at the protein level was rare: only a single amino acid in a gag p24 epitope showed convergence in the subtype B strains. Reversal of CTL-epitope mutations were also rare, and did not converge. Recombinant viruses were observed between the two subtype B strains. Luciferase-assays suggested that the CRF01_AE long terminal repeat (LTR) constituted the strongest promoter, but this was not reflected in the plasma viral load. Specific realtime PCR assays based upon the env gene showed that strain B2 and CRF01_AE RNA was present in equal amounts, while levels of strain B1 were 100-fold lower. All three strains were detected in seminal plasma, suggesting that simultaneous transmission is possible.
Examination of a Second Region of the HIV Type 1 Genome Reveals Additional Cases of Superinfection
AIDS Research and Human Retroviruses, 2008
HIV-1 superinfection may occur at a rate similar to that of initial infection, raising concerns for HIV-1 vaccine strategies predicated on eliciting immune responses similar to those in natural infection. Because of the high rate of recombination during HIV-1 replication, studies examining only one region of the HIV-1 genome are likely to miss cases of HIV-1 superinfection. We examined HIV-1 gag sequences from 14 high-risk Kenyan women in whom superinfection was not detected in a previous study of env sequences. We detected two additional cases of HIV-1 superinfection: one intersubtype superinfection that occurred between 1046 and 1487 days postinfection (DPI) and one intrasubtype superinfection that occurred between 341 and 440 DPI. Our results suggest that studies that examine only small genome regions may lead to underestimates of the risk of superinfection, highlighting the need for more extensive studies examining multiple regions of the HIV-1 genome.
Impaired Replication Capacity of Acute/Early Viruses in Persons Who Become HIV Controllers
Journal of Virology, 2010
Human immunodeficiency virus type 1 (HIV-1) controllers maintain viremia at <2,000 RNA copies/ml without antiretroviral therapy. Viruses from controllers with chronic infection were shown to exhibit impaired replication capacities, in part associated with escape mutations from cytotoxic-T-lymphocyte (CTL) responses. In contrast, little is known about viruses during acute/early infection in individuals who subsequently become HIV controllers. Here, we examine the viral replication capacities, HLA types, and virus sequences from 18 HIV-1 controllers identified during primary infection. g ag-protease chimeric viruses constructed using the earliest postinfection samples displayed significantly lower replication capacities than isolates from persons who failed to control viremia ( P = 0.0003). Protective HLA class I alleles were not enriched in these early HIV controllers, but viral sequencing revealed a significantly higher prevalence of drug resistance mutations associated with impa...
HIV-1 superinfection is not a common event
Journal of Clinical Virology, 2005
Evidence for human immunodeficiency virus type 1 (HIV-1) superinfection was investigated among a group of four previously HIV-1 infected transfusion recipients (and the four implicated HIV-1 infected donors) identified by the Transfusion Safety Study, and two groups of 4 and 5 Brazilian injection drug users, who consistently injected themselves using shared paraphernalia. To probe these cases for possible superinfection we used heteroduplex mobility analysis (HMA) of HIV-1 tat, a technique which is a reliable for establishing epidemiologic linkages and searching for minor strains in mixed infection settings. In all these cases with established, untreated HIV-1 infections, we were unable to detect HIV-1 superinfection, even though the involved individuals were at high risk for second strain acquisition. We therefore conclude that although superinfection can occur in a few cases, it is a rare event, and the vast majority of recombinant HIV-1s characterized to date resulted from acute coinfections, rather than superinfection.
Journal of Allergy and Clinical Immunology, 2003
During the past year, a number of reports have described HIV-1 superinfection in human subjects, defined as the reinfection of an individual with a second heterologous strain of HIV-1. These reports have challenged the assumption that HIV-1-specific immune responses generated during primary infection are protective against subsequent infection and have raised concern, not only with respect to HIV-1-positive individuals engaging in unsafe sex but also from the standpoint of developing effective vaccines. Herein we review the published reports of HIV-1 superinfection and highlight studies providing additional insight into the potential for HIV-1 superinfections to affect the global epidemic. (J Allergy Clin Immunol 2003;112:829-35.)