Comparative Analysis of Differential Cellular Transcriptome and Proteome Regulation by HIV-1 and HIV-2 Pseudovirions in the Early Phase of Infection
(2024) In International Journal of Molecular Sciences 25(1).- Abstract
In spite of the similar structural and genomic organization of human immunodeficiency viruses type 1 and 2 (HIV-1 and HIV-2), striking differences exist between them in terms of replication dynamics and clinical manifestation of infection. Although the pathomechanism of HIV-1 infection is well characterized, relatively few data are available regarding HIV-2 viral replication and its interaction with host–cell proteins during the early phase of infection. We utilized proteo-transcriptomic analyses to determine differential genome expression and proteomic changes induced by transduction with HIV-1/2 pseudovirions during 8, 12 and 26 h time-points in HEK-293T cells. We show that alteration in the cellular milieu was indeed different... (More)
In spite of the similar structural and genomic organization of human immunodeficiency viruses type 1 and 2 (HIV-1 and HIV-2), striking differences exist between them in terms of replication dynamics and clinical manifestation of infection. Although the pathomechanism of HIV-1 infection is well characterized, relatively few data are available regarding HIV-2 viral replication and its interaction with host–cell proteins during the early phase of infection. We utilized proteo-transcriptomic analyses to determine differential genome expression and proteomic changes induced by transduction with HIV-1/2 pseudovirions during 8, 12 and 26 h time-points in HEK-293T cells. We show that alteration in the cellular milieu was indeed different between the two pseudovirions. The significantly higher number of genes altered by HIV-2 in the first two time-points suggests a more diverse yet subtle effect on the host cell, preparing the infected cell for integration and latency. On the other hand, GO analysis showed that, while HIV-1 induced cellular oxidative stress and had a greater effect on cellular metabolism, HIV-2 mostly affected genes involved in cell adhesion, extracellular matrix organization or cellular differentiation. Proteomics analysis revealed that HIV-2 significantly downregulated the expression of proteins involved in mRNA processing and translation. Meanwhile, HIV-1 influenced the cellular level of translation initiation factors and chaperones. Our study provides insight into the understudied replication cycle of HIV-2 and enriches our knowledge about the use of HIV-based lentiviral vectors in general.
(Less)
- author
- Linkner, Tamás Richárd ; Ambrus, Viktor ; Kunkli, Balázs ; Szojka, Zsófia Ilona LU ; Kalló, Gergő ; Csősz, Éva ; Kumar, Ajneesh ; Emri, Miklós ; Tőzsér, József and Mahdi, Mohamed
- organization
- publishing date
- 2024
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- HIV-1, HIV-2, host response, infection, proteomic analysis, transcriptomic analysis
- in
- International Journal of Molecular Sciences
- volume
- 25
- issue
- 1
- article number
- 380
- publisher
- MDPI AG
- external identifiers
-
- pmid:38203551
- scopus:85181923454
- ISSN
- 1661-6596
- DOI
- 10.3390/ijms25010380
- language
- English
- LU publication?
- yes
- id
- 67729640-7cf4-403a-8a50-dc247c89ab2c
- date added to LUP
- 2024-02-13 12:26:30
- date last changed
- 2024-04-14 23:14:00
@article{67729640-7cf4-403a-8a50-dc247c89ab2c,
abstract = {{<p>In spite of the similar structural and genomic organization of human immunodeficiency viruses type 1 and 2 (HIV-1 and HIV-2), striking differences exist between them in terms of replication dynamics and clinical manifestation of infection. Although the pathomechanism of HIV-1 infection is well characterized, relatively few data are available regarding HIV-2 viral replication and its interaction with host–cell proteins during the early phase of infection. We utilized proteo-transcriptomic analyses to determine differential genome expression and proteomic changes induced by transduction with HIV-1/2 pseudovirions during 8, 12 and 26 h time-points in HEK-293T cells. We show that alteration in the cellular milieu was indeed different between the two pseudovirions. The significantly higher number of genes altered by HIV-2 in the first two time-points suggests a more diverse yet subtle effect on the host cell, preparing the infected cell for integration and latency. On the other hand, GO analysis showed that, while HIV-1 induced cellular oxidative stress and had a greater effect on cellular metabolism, HIV-2 mostly affected genes involved in cell adhesion, extracellular matrix organization or cellular differentiation. Proteomics analysis revealed that HIV-2 significantly downregulated the expression of proteins involved in mRNA processing and translation. Meanwhile, HIV-1 influenced the cellular level of translation initiation factors and chaperones. Our study provides insight into the understudied replication cycle of HIV-2 and enriches our knowledge about the use of HIV-based lentiviral vectors in general.</p>}},
author = {{Linkner, Tamás Richárd and Ambrus, Viktor and Kunkli, Balázs and Szojka, Zsófia Ilona and Kalló, Gergő and Csősz, Éva and Kumar, Ajneesh and Emri, Miklós and Tőzsér, József and Mahdi, Mohamed}},
issn = {{1661-6596}},
keywords = {{HIV-1; HIV-2; host response; infection; proteomic analysis; transcriptomic analysis}},
language = {{eng}},
number = {{1}},
publisher = {{MDPI AG}},
series = {{International Journal of Molecular Sciences}},
title = {{Comparative Analysis of Differential Cellular Transcriptome and Proteome Regulation by HIV-1 and HIV-2 Pseudovirions in the Early Phase of Infection}},
url = {{http://dx.doi.org/10.3390/ijms25010380}},
doi = {{10.3390/ijms25010380}},
volume = {{25}},
year = {{2024}},
}