Parallel Evolution in the V3 Region of HIV Type 1 after Infection of Hemophiliacs from a Homogeneous Source

Abstract

To determine the genetic diversification in the highly functional V3 loop, we followed up five hemophiliacs who were infected by a homogeneous HIV-1 population from a contaminated clotting factor lot. Initially, all patients displayed identical DNA sequences in this part of the proviral env gene. Therefore, this unique outbreak allows us to investigate the biological and genetic development of a common ancestor virus in different patients. A high degree of homology is maintained in the predominant sequences from 5 until 35 months after seroconversion. Only one patient showed a remarkable diversification 3 years postinfection. However, these genetic changes in the V3 region were not associated with disease progression. Discontinuous sequence changes were observed mainly in a region downstream of the V3 loop. Two positions in particular are involved in a sequence evolution within the V3 loop leading to the same amino acids in different patients. These directed changes occurred at sites that are reported to be critical for the specificity of antibodies (position 308) and viral cytopathicity (position 324). However, the parallel evolution was associated neither with differentiation of the viral phenotype nor with progression of the disease.

Fifteen years of Env C2V3C3 evolution in six individuals infected clonally with human immunodeficiency virus type 1

“…The C2V3C3 nucleotide sequence of the founder strain detected in the clotting factor served as reference for viral evolution. Shortly after seroconversion, the C2V3C3 nucleotide sequences showed 100% identity in all patients [Kasper et al, 1994]. In 15 years of HIV-1 infection, the highest rate of variability of the C2V3C3 amplicons was located within a portion of the so-called constant region C3, downstream of the V3 region, whereas the V3 loop-encoding sequence itself had comparatively low nucleotide variability (Fig.…”

“…However, PBMC cultivation of infectious virus from the clotting factor concentrate did not succeed. Sequence analyses of the hypervariable regions 1-3 of the HIV-env gene (V1-V3) showed an exceptionally high homogeneity (97.5-100% in the V1/ V2 region and 100% within the C2V3C3 region) of the viral sequences derived from the blood of the infected patients shortly after seroconversion [Cichutek et al, 1991;Kleim et al, 1991;Cichutek et al, 1992;Kasper et al, 1993;Kasper et al, 1994]. The detection of a homogeneous (without any ambiguities) C2V3C3 sequence in an archived sample of the suspected clotting factor lot identical to the patients' early C2V3C3 sequences revealed final evidence for the causal relationship between clotting factor consumption and the HIV-1 outbreak [Kupfer et al, 1995].…”

“…The goal of the present study was to analyze the evolution of the HIV-1 env C2V3C3 region in six clonally infected hemophiliacs over a time period of up to 15 years. These hemophilia B patients were infected from one unique clotting factor lot containing a genetically homogeneous HIV-1 population [Kupfer et al, 1995], an incident that allowed the follow-up of viral evolution starting from a single founder strain in different human hosts [Kasper et al, 1993;Kasper et al, 1994;Kasper et al, 1995].…”

A Small Set of Succinct Signature Patterns Distinguishes Chinese and Non-Chinese HIV-1 Genomes

“…The existence of such HIV-1 variants is relevant to the treatment of infected individuals and to the development of vaccines [2], [3]. Moreover, tracking of variants can be used to discover routes of infection [4]. Last but not least it is interesting to follow viral evolution and to explore the underlying evolutionary phenomena.…”

Sequence Note: Genetic Characterization of the V3 Loop Sequences of 21 HIV Type 1 Spanish Isolates from Hemophilia Patients

“…Other known motifs are GPGK (19%), GPGG (9.5%), and GPGS (4.5%), all of which have been previously reported in different B subtypes from European hemophiliac patients. [3][4][5][6] To obtain more detailed information on the evolution of HIV-…”