Biomedical subjects

A Birdwell

Publications and source records attributed to A Birdwell.

3 recordsLinked to original sources

PubMed1995

Nef and LTR sequence variation from sequentially derived human immunodeficiency virus type 1 isolates.

Variation in HIV-1 nef and LTR DNA sequences was assessed longitudinally during disease progression in four HIV-1-infected subjects. Point mutations were found among quasispecies obtained at a single time point in each individual, with increasing diversity with disease progression in two of three patients for whom sufficient data were available for analysis. Deletions and rearrangements were more common in late than early stages of disease. Continued sequence evolution in HIV-1 quasispecies with nef deletions along with coexistence of nef-bearing quasispecies suggest that nef-deleted quasispecies are capable of replication in vivo, possibly complemented by quasispecies lacking such deletions and/or by adaptation to a specialized niche within the patients.

Amino Acid Sequence↗

PubMed1993

Evolution of sequence divergence among human immunodeficiency virus type 1 isolates derived from a blood donor and a recipient.

Four neonates who were infected with a single unit of blood from a human immunodeficiency virus-1 (HIV-1)-infected adult (patient 1) were studied. Two of the infected children (patients II and III) developed symptomatic HIV-1 disease and died within the first 3 y of life. One child (patient IV) died at 8 mo of age of clinical problems that may have been HIV-related. In contrast, one child (patient V) has remained asymptomatic for 7.5 y and has exhibited a very gradual decline in CD4+ cell number. A previous study had shown very limited sequence diversity of isolates from patients I, II, and III (McNearney T et al.: Proc Natl Acad Sci USA 87:1917-1921, 1990). The current study examined additional HIV-1 sequences encoding the principal neutralizing V3 loop of the surface envelope protein of isolates from patients I and V. Amplified sequences were obtained using the polymerase chain reaction from a cultured isolate and uncultured peripheral blood leukocytes, and nucleotide sequences were determined for 13 clones from patient I and 19 clones from patient V. Clones derived from the cultured isolate exhibited less predicted amino acid sequence diversity on average (0-5.2%) than did sequences from uncultured leukocytes (0-19.8% differences). All clones were more closely related to those from patients II and III (0-19.8% amino acid differences) than to other North American or European isolates (18.8-27.0% amino acid differences) or African isolates (41.0-48.0% amino acid differences). Substitutions occurred at sites predicted to modulate host cell tropism and proteolytic cleavage of the V3 loop.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Relationship of human immunodeficiency virus type 1 sequence heterogeneity to stage of disease.

V3 envelope sequences were determined from amplified human immunodeficiency virus type 1 (HIV-1) sequences of uncultivated leukocytes obtained sequentially from four infected adults over the course of infection. Lower levels of sequence heterogeneity were noted in samples obtained early in HIV-1 infection, prior to CD4 depletion, than in samples obtained at later times during disease. The pattern of amino acid sequence divergence included nonrandom changes, with evidence of sequence variants arising from HIV-1 quasi-species present earlier in infection. Consensus sequences for isolates obtained early after infection from different patients demonstrated a high level of conservation with one another and a consensus sequence for macrophage-tropic HIV-1 isolates. These findings suggest that a highly restricted subset of HIV-1 quasi-species can be transmitted and can establish infection.

Acquired Immunodeficiency Syndrome↗