Defective accessory genes in a human immunodeficiency virus type 1-infected long-term survivor lacking recoverable virus

  title={Defective accessory genes in a human immunodeficiency virus type 1-infected long-term survivor lacking recoverable virus},
  author={Nelson L. Michael and George Chang and L A d'Arcy and Philip K. Ehrenberg and Roberto Mariani and Marc Busch and Deborah L. Birx and David H. Schwartz},
  journal={Journal of Virology},
  pages={4228 - 4236}
We have been studying a patient who acquired human immunodeficiency virus (HIV) infection via a blood transfusion 13 years ago. She has remained asymptomatic since that time. The blood donor and two other recipients have all died of AIDS. Although this patient has shown persistently strong seroreactivity to HIV type 1 (HIV-1) antigens by Western blot (immunoblot), she has been continually HIV culture negative in results from multiple laboratories over the last 6 years and has a very low viral… 

Potential Contributions of Viral Envelope and Host Genetic Factors in a Human Immunodeficiency Virus Type 1-Infected Long-Term Survivor

The data suggest that the changes in envelope sequences confer properties of viral attenuation, which together with the CCR5 +/Δ32 genotype could account for the long-term survival of this patient.

Grossly Defective nef Gene Sequences in a Human Immunodeficiency Virus Type 1-Seropositive Long-Term Nonprogressor

The existence of a similar condition in a subject who acquired HIV-1 seropositivity through the sexual route is shown, and length polymorphism analysis suggested the existence of two major quasispecies populations.

Characterization of Three nef-Defective Human Immunodeficiency Virus Type 1 Strains Associated with Long-Term Nonprogression

Three HIV-1-infected individuals in Australia who have been infected for over 11 years with viruses that contain deletions in the nef and nef-long terminal repeat (nef/LTR) overlap regions are identified.

Genotypic and phenotypic characterization of long terminal repeat sequences from long-term survivors of human immunodeficiency virus type 1 infection

Functional abnormalities were found in the LTR from Pt 5 in directing both heterologous and viral gene expression, providing a possible genetic explanation for the low viral load and prolonged asymptomatic state of this individual.

Characterization of human immunodeficiency virus type 1 vif gene in long-term asymptomatic individuals.

While the replication properties in the SupT1 cell line were unmodified, the mutagenized virus revealed a fivefold decreased replication in activated PBMC, suggesting a possible role of this Vif signature for viral production in vivo.

Characterization of the functional properties of env genes from long-term survivors of human immunodeficiency virus type 1 infection

The functional activity of env clones from long-term survivors D and DH was comparable to that seen with several primary HIV-1 env genes cloned from individuals with disease progression and AIDS, suggesting that functional abnormalities in env may contribute to maintaining a long- term asymptomatic state in the other four cases the authors studied.

Persistent Antibody Responses but Declining Cytotoxic T-Lymphocyte Responses to Multiple Human Immunodeficiency Virus Type 1 Antigens in a Long-Term Nonprogressing Individual with a Defective p17 Proviral Sequence and No Detectable Viral RNA Expression

Cytotoxic T-lymphocyte responses to Env and Gag antigens have gradually diminished over the past 4 years, at a time when the titers of antibodies to the same proteins have remained stable, and what these observations might mean for the generation and maintenance of immunological memory.

Isolation and Characterization of Replication-Competent Human Immunodeficiency Virus Type 1 from a Subset of Elite Suppressors

The results suggest that some ES are infected with HIV-1 isolates that are fully replication competent and that long-term immunologic control of replication-competent HIV- 1 is possible.

Long-term nonprogressive infection with human immunodeficiency virus type 1 in a hemophilia cohort.

LTNPs in this cohort have maintained remarkably low virus burdens and vigorous HIV-1-specific cell-mediated immunity over a 15-year period, and the presence of expanded, activated CD8 T cells with cytotoxic effector function in the peripheral blood suggests ongoing viral replication.

Nuclear localization of HIV type 1 Vif isolated from a long-term asymptomatic individual and potential role in virus attenuation.

The viral isolate from an HIV-1-infected long-term nonprogressor that displayed a Vif-mutant replication phenotype was studied and provided a unique tool to investigate the interaction of Vif and Apobec3G.



Absence of recoverable infectious virus and unique immune responses in an asymptomatic HIV+ long-term survivor.

We have studied a woman with transfusion-acquired HIV who appears to have contained infectious virus to consistently undetectable levels over a 13-year period without antiviral treatment. She

Characterization of nef sequences in long-term survivors of human immunodeficiency virus type 1 infection

Examination of the nef gene in 10 patients who are clinically healthy and immunologically normal despite 12 to 15 years of infection finds that deletion of or gross sequence abnormality within nef is not likely to be a common explanation for the well-being of long-term survivors of HIV-1 infection.

Normal immune function and inability to isolate virus in culture in an individual with long-term human immunodeficiency virus type 1 infection.

In this individual, the combination of low viral load in the peripheral blood and a strong, responsive immune system is associated with long-term, disease-free coexistence with HIV-1 infection.

Nef from primary isolates of human immunodeficiency virus type 1 suppresses surface CD4 expression in human and mouse T cells

The ability to suppress cell surface CD4 expression is an intrinsic feature of HIV-1 Nef, and an artificially generated consensus nef gene derived from analysis of 54 patient isolates ofAIDS is tested.

Human immunodeficiency virus type 1 Vpu has a CD4- and an envelope glycoprotein-independent function

It is shown that the lack of expression of intact Vpu results in a 90% reduction in infectious virus produced over a single round of replication from HeLa cells in the absence of CD4 expression.

Vif is crucial for human immunodeficiency virus type 1 proviral DNA synthesis in infected cells

The results suggest that Vif plays a role which is novel for a retroviral protein, in allowing the processing and/or the transport of the internalized HIV core.

Detection of replication-competent and pseudotyped human immunodeficiency virus with a sensitive cell line on the basis of activation of an integrated beta-galactosidase gene

We have constructed a HeLa cell line that both expresses high levels of CD4 and contains a single integrated copy of a beta-galactosidase gene that is under the control of a truncated human

Cell-free transmission of Vif mutants of HIV-1.

Naturally occurring genotypes of the human immunodeficiency virus type 1 long terminal repeat display a wide range of basal and Tat-induced transcriptional activities

A longitudinal analysis of molecular clones from the LTR/gag leader region amplified directly from the peripheral blood of four patients over three years found a remarkable number of point mutations and length polymorphisms in cis- and trans-acting regulatory elements within this cohort.

Downregulation of cell-surface CD4 expression by simian immunodeficiency virus Nef prevents viral super infection

It is hypothesized that downregulation of cell-surface CD4 by Nef facilitates the efficient release of infectious progeny virions and, hence, viral spread in vivo.