Evolution of syncytium-inducing and non-syncytium-inducing biological virus clones in relation to replication kinetics during the course of human immunodeficiency virus type 1 infection - PubMed (original) (raw)

Evolution of syncytium-inducing and non-syncytium-inducing biological virus clones in relation to replication kinetics during the course of human immunodeficiency virus type 1 infection

A B van 't Wout et al. J Virol. 1998 Jun.

Abstract

To investigate the temporal relationship between human immunodeficiency virus type 1 (HIV-1) replicative capacity and syncytium-inducing (SI) phenotype, biological and genetic characteristics of longitudinally obtained virus clones from two HIV-1-infected individuals who developed SI variants were studied. In one individual, the emergence of rapidly replicating SI and non-syncytium-inducing (NSI) variants was accompanied by a loss of the slowly replicating NSI variants. In the other subject, NSI variants were always slowly replicating, while the coexisting SI variants showed an increase in the rate of replication. Irrespective their replicative capacity, the NSI variants remained present throughout the infection in both individuals. Phylogenetic analysis of the V3 region showed early branching of the SI variants from the NSI tree. Successful SI conversion seemed a unique event since no SI variants were found among later-stage NSI variants. This was also confirmed by the increasing evolutionary distance between the two subpopulations. At any time point during the course of the infection, the variation within the coexisting SI and NSI populations did not exceed 2%, indicating continuous competition within each viral subpopulation.

PubMed Disclaimer

Figures

FIG. 1

FIG. 1

Replication kinetics of SI (•) and NSI (○) HIV-1 clones during the course of HIV-1 infection in two subjects harboring both SI and NSI virus variants. From each virus clone, 103 TCID50 was added to 5 × 106 2-day PHA-stimulated PBMC derived from the same donor on which the titer was determined. After 5, 8, and 11 days, approximately 3 × 106 fresh stimulated target cells were added. Samples (75 μl) for determination of p24 production were harvested every day after infection for 14 days. Each line represents the results obtained for one virus clone; ▸ indicates NSI clone 12B3 with arginines at positions 10 and 25. AIDS diagnosis for ACH0039 and ACH0208 was at 37 and 54 months respectively, postseroconversion (post sc.).

FIG. 2

FIG. 2

Replication kinetics of SI (•) and NSI (○) HIV-1 clones in four subjects at the time of AIDS diagnosis. From each virus clone, 103 TCID50 was added to 5 × 106 2-day PHA-stimulated PBMC derived from the same donor on which the titer was determined. After 5, 8, and 11 days, approximately 3 × 106 fresh stimulated target cells were added. Samples (75 μl) for determination of p24 production were harvested every day after infection for 14 days. Means and standard errors of the results for four to five virus clones per phenotype are shown.

FIG. 3

FIG. 3

Changes in infectious cellular SI (▪) and NSI (□) HIV-1 load in relation to time after seroconversion or seropositive entry. The frequency of cells productively infected with NSI or SI variants was determined by limiting-dilution analysis of patient PBMC on PHA-stimulated target cells.

FIG. 4

FIG. 4

Deduced amino acid sequences of the V3 region. The sequences are aligned with the consensus sequence of the variants present in the first sample for each patient. Amino acid positions involved in SI capacity are marked (↓). Dashes indicate identity with the reference sequence. , silent mutation compared with reference sequence. (A) Alignment of V3 sequences from virus clones obtained during the course of infection of participant ACH0039. Position 1 corresponds to amino acid 268 of the HXB2 envelope protein. (B) Alignment of V3 sequences from virus clones obtained during the course of infection of participant ACH0208. Position 1 corresponds to amino acid 296 of the HXB2 envelope protein.

FIG. 5

FIG. 5

Plots of synonymous (dS) and nonsynonymous (dN) substitution rates in the V3 region of the virus clones obtained in the course of HIV-1 infection from two subjects, ACH0039 (A) and ACH0208 (B). Estimation of the number of silent and nonsilent substitutions between all sequences from one time point and the consensus sequence of that time point was done according to Nei and Gojobori’s method (36) as implemented in MEGA (31). Numbers of synonymous (○) and nonsynonymous (•) substitutions from the same time point are shown. ∗, P = 0.0040.

FIG. 6

FIG. 6

Results of phylogenetic analysis of the V3 region (neighbor-joining method, unrooted tree) from virus clones obtained during the course of infection of participants ACH0039 and ACH0208. Bootstrap values indicate the percentages of trees showing the observed specific groupings. Filled symbols, SI sequences; open symbols, NSI sequences.

FIG. 7

FIG. 7

Plots of Hamming distances for the V3 region between the virus clones obtained in the course of HIV-1 infection from two subjects, ACH0039 (A) and ACH0208 (B). Distances were calculated by using DNADIST as implemented in the PHYLIP program. Comparisons between NSI variants, between SI variants, and between SI and NSI variants from the same time point are shown.

Similar articles

Cited by

References

    1. Alkhatib G, Combadiere C, Broder C C, Feng Y, Kennedy P E, Murphy P M, Berger E A. CC CKR5: a RANTES, MIP-1α, MIP-1β receptor as a fusion cofactor for macrophage-tropic HIV-1. Science. 1996;272:1955–1958. - PubMed
    1. Åsjö B, Albert J, Karlsson A, Morfeldt-Månson L, Biberfeld G, Lidman K, Fenyö E M. Replicative capacity of human immunodeficiency virus from patients with varying severity of HIV infection. Lancet. 1986;ii:660–662. - PubMed
    1. Balliet J W, Kolson D L, Eiger G, Kim F M, MacGann K A, Srinivasan A, Collman R. Distinct effects in primary macrophages and lymphocytes of the human immunodeficiency virus type 1 accessory genes vpr, vpu, and nef: mutational analysis of a primary HIV-1 isolate. Virology. 1994;200:623–631. - PubMed
    1. Blaak, H. Unpublished observations.
    1. Boom R, Sol C J A, Salimans M M M, Jansen C L, Wertheim-van Dillen P M E, Van der Noordaa J. A rapid and simple method for purification of nucleic acids. J Clin Microbiol. 1991;28:495–503. - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources