Modulation of Different Human Immunodeficiency Virus Type 1 Nef Functions During Progression to AIDS

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2001 Mar 27

PMID 11264355

Citations 81

Authors

S Carl

T C Greenough

M Krumbiegel

M Greenberg

J Skowronski

J L Sullivan

F Kirchhoff

Affiliations

Soon will be listed here.

Abstract

The human immunodeficiency virus type 1 (HIV-1) Nef protein has several independent functions that might contribute to efficient viral replication in vivo. Since HIV-1 adapts rapidly to its host environment, we investigated if different Nef properties are associated with disease progression. Functional analysis revealed that nef alleles obtained during late stages of infection did not efficiently downmodulate class I major histocompatibility complex but were highly active in the stimulation of viral replication. In comparison, functional activity in downregulation of CD4 and enhancement of HIV-1 infectivity were maintained or enhanced after AIDS progression. Our results demonstrate that various Nef activities are modulated during the course of HIV-1 infection to maintain high viral loads at different stages of disease progression. These findings suggest that all in vitro Nef functions investigated contribute to AIDS pathogenesis and indicate that nef variants with increased pathogenicity emerge in a significant number of HIV-1-infected individuals.

Citing Articles

Nef mediates neuroimmune response, myelin impairment, and neuronal injury in EcoHIV-infected mice.

Schenck J, Clarkson-Paredes C, Pushkarsky T, Wang Y, Miller R, Bukrinsky M Life Sci Alliance. 2024; 8(2).

PMID: 39532531 PMC: 11557684. DOI: 10.26508/lsa.202402879.

HIV Productively Infects Highly Differentiated and Exhausted CD4+ T Cells During AIDS.

Faua C, Ursenbach A, Fuchs A, Caspar S, Jegou F, Ruch Y Pathog Immun. 2024; 8(2):92-114.

PMID: 38420260 PMC: 10901154. DOI: 10.20411/pai.v8i2.638.

HIV-1 subtype C Nef-mediated SERINC5 down-regulation significantly contributes to overall Nef activity.

Naicker D, Sonela N, Jin S, Mulaudzi T, Ojwach D, Reddy T Retrovirology. 2023; 20(1):3.

PMID: 37004071 PMC: 10067162. DOI: 10.1186/s12977-023-00618-7.

Nef enhances HIV-1 replication and infectivity independently of SERINC5 in CEM T cells.

Ramirez P, Vollbrecht T, Acosta F, Suarez M, Angerstein A, Wallace J Virology. 2022; 578:154-162.

PMID: 36577173 PMC: 10484624. DOI: 10.1016/j.virol.2022.12.008.

HIV-1 Nef-mediated downregulation of CD155 results in viral restriction by KIR2DL5+ NK cells.

Fittje P, Hoelzemer A, Garcia-Beltran W, Vollmers S, Niehrs A, Hagemann K PLoS Pathog. 2022; 18(6):e1010572.

PMID: 35749424 PMC: 9231786. DOI: 10.1371/journal.ppat.1010572.

References

Greenough T, Brettler D, Kirchhoff F, Alexander L, Desrosiers R, OBrien S . Long-term nonprogressive infection with human immunodeficiency virus type 1 in a hemophilia cohort. J Infect Dis. 1999; 180(6):1790-802. DOI: 10.1086/315128. View

Desrosiers R . Strategies used by human immunodeficiency virus that allow persistent viral replication. Nat Med. 1999; 5(7):723-5. DOI: 10.1038/10439. View

Swigut T, Iafrate A, MUENCH J, Kirchhoff F, Skowronski J . Simian and human immunodeficiency virus Nef proteins use different surfaces to downregulate class I major histocompatibility complex antigen expression. J Virol. 2000; 74(12):5691-701. PMC: 112057. DOI: 10.1128/jvi.74.12.5691-5701.2000. View

Iafrate A, Carl S, Bronson S, Stahl-Hennig C, Swigut T, Skowronski J . Disrupting surfaces of nef required for downregulation of CD4 and for enhancement of virion infectivity attenuates simian immunodeficiency virus replication in vivo. J Virol. 2000; 74(21):9836-44. PMC: 102020. DOI: 10.1128/jvi.74.21.9836-9844.2000. View

Fultz P, McClure H, Anderson D, Switzer W . Identification and biologic characterization of an acutely lethal variant of simian immunodeficiency virus from sooty mangabeys (SIV/SMM). AIDS Res Hum Retroviruses. 1989; 5(4):397-409. DOI: 10.1089/aid.1989.5.397. View

Crise B, Buonocore L, Rose J . CD4 is retained in the endoplasmic reticulum by the human immunodeficiency virus type 1 glycoprotein precursor. J Virol. 1990; 64(11):5585-93. PMC: 248611. DOI: 10.1128/JVI.64.11.5585-5593.1990. View

Garcia J, Miller A . Serine phosphorylation-independent downregulation of cell-surface CD4 by nef. Nature. 1991; 350(6318):508-11. DOI: 10.1038/350508a0. View

Kestler 3rd H, Ringler D, Mori K, Panicali D, Sehgal P, Daniel M . Importance of the nef gene for maintenance of high virus loads and for development of AIDS. Cell. 1991; 65(4):651-62. DOI: 10.1016/0092-8674(91)90097-i. View

Willey R, Maldarelli F, Martin M, Strebel K . Human immunodeficiency virus type 1 Vpu protein induces rapid degradation of CD4. J Virol. 1992; 66(12):7193-200. PMC: 240416. DOI: 10.1128/JVI.66.12.7193-7200.1992. View

10.

Skowronski J, Parks D, Mariani R . Altered T cell activation and development in transgenic mice expressing the HIV-1 nef gene. EMBO J. 1993; 12(2):703-13. PMC: 413256. DOI: 10.1002/j.1460-2075.1993.tb05704.x. View

11.

BENSON R, Sanfridson A, Ottinger J, Doyle C, Cullen B . Downregulation of cell-surface CD4 expression by simian immunodeficiency virus Nef prevents viral super infection. J Exp Med. 1993; 177(6):1561-6. PMC: 2191034. DOI: 10.1084/jem.177.6.1561. View

12.

Miller M, Warmerdam M, Gaston I, Greene W, Feinberg M . The human immunodeficiency virus-1 nef gene product: a positive factor for viral infection and replication in primary lymphocytes and macrophages. J Exp Med. 1994; 179(1):101-13. PMC: 2191317. DOI: 10.1084/jem.179.1.101. View

13.

Spina C, Kwoh T, Chowers M, Guatelli J, Richman D . The importance of nef in the induction of human immunodeficiency virus type 1 replication from primary quiescent CD4 lymphocytes. J Exp Med. 1994; 179(1):115-23. PMC: 2191324. DOI: 10.1084/jem.179.1.115. View

14.

Chowers M, Spina C, Kwoh T, Fitch N, Richman D, Guatelli J . Optimal infectivity in vitro of human immunodeficiency virus type 1 requires an intact nef gene. J Virol. 1994; 68(5):2906-14. PMC: 236779. DOI: 10.1128/JVI.68.5.2906-2914.1994. View

15.

Greenough T, Somasundaran M, Brettler D, Hesselton R, Alimenti A, Kirchhoff F . Normal immune function and inability to isolate virus in culture in an individual with long-term human immunodeficiency virus type 1 infection. AIDS Res Hum Retroviruses. 1994; 10(4):395-403. DOI: 10.1089/aid.1994.10.395. View

16.

Tovo P, De Martino M, Gabiano C, Galli L, Tibaldi C, Vierucci A . AIDS appearance in children is associated with the velocity of disease progression in their mothers. J Infect Dis. 1994; 170(4):1000-2. DOI: 10.1093/infdis/170.4.1000. View

17.

Kirchhoff F, Greenough T, Brettler D, Sullivan J, Desrosiers R . Brief report: absence of intact nef sequences in a long-term survivor with nonprogressive HIV-1 infection. N Engl J Med. 1995; 332(4):228-32. DOI: 10.1056/NEJM199501263320405. View

18.

Wei X, Ghosh S, Taylor M, Johnson V, Emini E, Deutsch P . Viral dynamics in human immunodeficiency virus type 1 infection. Nature. 1995; 373(6510):117-22. DOI: 10.1038/373117a0. View

19.

Ho D, Neumann A, Perelson A, Chen W, Leonard J, Markowitz M . Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature. 1995; 373(6510):123-6. DOI: 10.1038/373123a0. View

20.

Deacon N, Tsykin A, Solomon A, Smith K, Hooker D, McPhee D . Genomic structure of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients. Science. 1995; 270(5238):988-91. DOI: 10.1126/science.270.5238.988. View