Endogenous Retroviral Envelope Syncytin Induces HIV-1 Spreading and Establishes HIV Reservoirs in Placenta

Tang, Yuyang; Woodward, Beverly; Pastor, Lorena; George, Alvin M.; Petrechko, Oksana; Nouvet, Franklin J.; Haas, David W.; Jiang, Guochun; Hildreth, James E. K.

doi:10.1016/j.celrep.2020.03.016

Cited by 29 publications

(16 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HIV-1 was shown to hijack other viral Envs to directly enter CD4-negative cells through pseudotyping [ 80 , 81 , 82 ]. Lately, Tang Y. et al have shown that HIV-1 infected T cells can fuse to and transfer the virus to placental trophoblasts, if the later express on their surfaces the envelope glycoprotein of human endogenous retrovirus family W1, syncytin [ 83 ]. This leads to the formation of an HIV-1 reservoir in the epithelial cells [ 83 ].…”

Section: Mechanisms Underlying Hiv-1 Pathogenicity In Epithelial Cmentioning

confidence: 99%

“…Lately, Tang Y. et al have shown that HIV-1 infected T cells can fuse to and transfer the virus to placental trophoblasts, if the later express on their surfaces the envelope glycoprotein of human endogenous retrovirus family W1, syncytin [ 83 ]. This leads to the formation of an HIV-1 reservoir in the epithelial cells [ 83 ]. Syncytin-1 derives from a family of endogenous retroviruses and originates from HERVW1 infection of human germ cells [ 84 ].…”

Section: Mechanisms Underlying Hiv-1 Pathogenicity In Epithelial Cmentioning

confidence: 99%

See 1 more Smart Citation

Oncogenic Effects of HIV-1 Proteins, Mechanisms Behind

Isaguliants

Bayurova

Avdoshina

et al. 2021

Cancers

View full text Add to dashboard Cite

People living with human immunodeficiency virus (HIV-1) are at increased risk of developing cancer, such as Kaposi sarcoma (KS), non-Hodgkin lymphoma (NHL), cervical cancer, and other cancers associated with chronic viral infections. Traditionally, this is linked to HIV-1-induced immune suppression with depletion of CD4+ T-helper cells, exhaustion of lymphopoiesis and lymphocyte dysfunction. However, the long-term successful implementation of antiretroviral therapy (ART) with an early start did not preclude the oncological complications, implying that HIV-1 and its antigens are directly involved in carcinogenesis and may exert their effects on the background of restored immune system even when present at extremely low levels. Experimental data indicate that HIV-1 virions and single viral antigens can enter a wide variety of cells, including epithelial. This review is focused on the effects of five viral proteins: envelope protein gp120, accessory protein negative factor Nef, matrix protein p17, transactivator of transcription Tat and reverse transcriptase RT. Gp120, Nef, p17, Tat, and RT cause oxidative stress, can be released from HIV-1-infected cells and are oncogenic. All five are in a position to affect “innocent” bystander cells, specifically, to cause the propagation of (pre)existing malignant and malignant transformation of normal epithelial cells, giving grounds to the direct carcinogenic effects of HIV-1.

show abstract

Section: Mechanisms Underlying Hiv-1 Pathogenicity In Epithelial Cmentioning

confidence: 99%

Section: Mechanisms Underlying Hiv-1 Pathogenicity In Epithelial Cmentioning

confidence: 99%

Oncogenic Effects of HIV-1 Proteins, Mechanisms Behind

Isaguliants

Bayurova

Avdoshina

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…For example, HIV-1 infection results in the transcription and translation of HERV-K (HML-2) loci, representing the youngest ERV family in humans ( 14 , 19–25 ). Several follow-up studies focused on the induction of cellular and humoral immune responses against HERV-K (HML-2) proteins in HIV-1 infected individuals ( 26–30 ) and a possible interference of ERV proteins with HIV ( 31–33 ). In contrast, the impact of HIV-1 infection on regulatory ERV elements and their downstream effects on cellular gene expression remained unclear.…”

Section: Introductionmentioning

confidence: 99%

HIV-1 infection activates endogenous retroviral promoters regulating antiviral gene expression

Badarinarayan

Shcherbakova

Langer

et al. 2020

Nucleic Acids Research

View full text Add to dashboard Cite

Although endogenous retroviruses (ERVs) are known to harbor cis-regulatory elements, their role in modulating cellular immune responses remains poorly understood. Using an RNA-seq approach, we show that several members of the ERV9 lineage, particularly LTR12C elements, are activated upon HIV-1 infection of primary CD4+ T cells. Intriguingly, HIV-1-induced ERVs harboring transcription start sites are primarily found in the vicinity of immunity genes. For example, HIV-1 infection activates LTR12C elements upstream of the interferon-inducible genes GBP2 and GBP5 that encode for broad-spectrum antiviral factors. Reporter assays demonstrated that these LTR12C elements drive gene expression in primary CD4+ T cells. In line with this, HIV-1 infection triggered the expression of a unique GBP2 transcript variant by activating a cryptic transcription start site within LTR12C. Furthermore, stimulation with HIV-1-induced cytokines increased GBP2 and GBP5 expression in human cells, but not in macaque cells that naturally lack the GBP5 gene and the LTR12C element upstream of GBP2. Finally, our findings suggest that GBP2 and GBP5 have already been active against ancient viral pathogens as they suppress the maturation of the extinct retrovirus HERV-K (HML-2). In summary, our findings uncover how human cells can exploit remnants of once-infectious retroviruses to regulate antiviral gene expression.

show abstract

“…Notably, the incorporation of ERV-derived gene products into exogenous viral particles may not always negatively interfere with their assembly or infectivity. For example, certain HERV-derived protease (75,76), integrase (77) or Env (78,79) proteins may at least partially complement HIV-1 mutants with defects in the respective genes and sometimes even expanded the tropism to CD4+ negative cells (78,79). Nevertheless, the co-option of retroviral genes to negatively interfere with virion production represents a simple yet effective antiviral mechanism that has evolved several times independently during mammalian evolution.…”

Section: Downloaded Frommentioning

confidence: 99%

Switching Sides: How Endogenous Retroviruses Protect Us from Viral Infections

Badarinarayan

Sauter

2021

J Virol

View full text Add to dashboard Cite

Long disregarded as junk DNA or genomic dark matter, endogenous retroviruses (ERVs) turned out to represent important components of the antiviral immune response. These remnants of once-infectious retroviruses not only regulate cellular immune activation, but may even directly target invading viral pathogens. In this review, we summarize mechanisms, by which retroviral fossils protect us from viral infections. One focus will be on recent advances in the role of ERVs as regulators of antiviral gene expression.

show abstract

Endogenous Retroviral Envelope Syncytin Induces HIV-1 Spreading and Establishes HIV Reservoirs in Placenta

Cited by 29 publications

References 63 publications

Oncogenic Effects of HIV-1 Proteins, Mechanisms Behind

Oncogenic Effects of HIV-1 Proteins, Mechanisms Behind

HIV-1 infection activates endogenous retroviral promoters regulating antiviral gene expression

Switching Sides: How Endogenous Retroviruses Protect Us from Viral Infections

Contact Info

Product

Resources

About