HIV-1 genomic rna diversification following sexual and parenteral virus transmission

Virology ◽  
1992 ◽  
Vol 189 (1) ◽  
pp. 103-110 ◽  
Author(s):  
Tom F.W. Wolfs ◽  
Gabriël Zwart ◽  
Margreet Bakker ◽  
Jaap Goudsmit
Keyword(s):  
Author(s):  
Bernadien M. Nijmeijer ◽  
Marta Bermejo-Jambrina ◽  
Tanja M. Kaptein ◽  
Carla M. S. Ribeiro ◽  
Doris Wilflingseder ◽  
...  

AbstractSemen is important in determining HIV-1 susceptibility but it is unclear how it affects virus transmission during sexual contact. Mucosal Langerhans cells (LCs) are the first immune cells to encounter HIV-1 during sexual contact and have a barrier function as LCs are restrictive to HIV-1. As semen from people living with HIV-1 contains complement-opsonized HIV-1, we investigated the effect of complement on HIV-1 dissemination by human LCs in vitro and ex vivo. Notably, pre-treatment of HIV-1 with semen enhanced LC infection compared to untreated HIV-1 in the ex vivo explant model. Infection of LCs and transmission to target cells by opsonized HIV-1 was efficiently inhibited by blocking complement receptors CR3 and CR4. Complement opsonization of HIV-1 enhanced uptake, fusion, and integration by LCs leading to an increased transmission of HIV-1 to target cells. However, in the absence of both CR3 and CR4, C-type lectin receptor langerin was able to restrict infection of complement-opsonized HIV-1. These data suggest that complement enhances HIV-1 infection of LCs by binding CR3 and CR4, thereby bypassing langerin and changing the restrictive nature of LCs into virus-disseminating cells. Targeting complement factors might be effective in preventing HIV-1 transmission.


Biopolymers ◽  
2003 ◽  
Vol 69 (1) ◽  
pp. 1-14 ◽  
Author(s):  
G. La Penna ◽  
D. Genest ◽  
A. Perico
Keyword(s):  

2002 ◽  
Vol 76 (20) ◽  
pp. 10444-10454 ◽  
Author(s):  
Jielin Zhang ◽  
Clyde S. Crumpacker

ABSTRACT An important aspect of the pathophysiology of human immunodeficiency virus type 1 (HIV-1) infection is the ability of the virus to replicate in the host vigorously without a latent phase and to kill cells with a dynamic turnover of 1.8 × 109 cells/day and 10.3 × 109 virions/24 h. The transcription of HIV-1 RNA in acute infection occurs at two stages; the transcription of viral spliced mRNA occurs early, and the transcription of viral genomic RNA occurs later. The HIV-1 Tat protein is translated from the early spliced mRNA and is critical for HIV-1 genomic RNA expression. The cellular transcription factors are important for HIV-1 early spliced mRNA expression. In this study we show that virion nucleocapsid protein (NC) has a role in expression of HIV-1 early spliced mRNA. The HIV-1 NC migrates from the cytoplasm to the nucleus and accumulates in the nucleus at 18 h postinfection. Mutations on HIV-1 NC zinc fingers change the pattern of early viral spliced mRNA expression and result in a delayed expression of early viral mRNA in HIV-infected cells. This delayed HIV-1 early spliced mRNA expression occurs after proviral DNA has been integrated into the cellular genome, as shown by a quantitative integration assay. These results show that virion NC plays an important role in inducing HIV-1 early mRNA expression and contributes to the rapid viral replication that occurs during HIV-1 infection.


2008 ◽  
Vol 47 (22) ◽  
pp. 4110-4113 ◽  
Author(s):  
Séverine Freisz ◽  
Kathrin Lang ◽  
Ronald Micura ◽  
Philippe Dumas ◽  
Eric Ennifar

2002 ◽  
Vol 76 (15) ◽  
pp. 7812-7821 ◽  
Author(s):  
Rogier W. Sanders ◽  
Esther C. de Jong ◽  
Christopher E. Baldwin ◽  
Joost H. N. Schuitemaker ◽  
Martien L. Kapsenberg ◽  
...  

ABSTRACT Dendritic cells (DC) support human immunodeficiency virus type 1 (HIV-1) transmission by capture of the virus particle in the mucosa and subsequent transport to the draining lymph node, where HIV-1 is presented to CD4+ Th cells. Virus transmission involves a high-affinity interaction between the DC-specific surface molecule DC-SIGN and the viral envelope glycoprotein gp120 and subsequent internalization of the virus, which remains infectious. The mechanism of viral transmission from DC to T cells is currently unknown. Sentinel immature DC (iDC) develop into Th1-promoting effector DC1 or Th2-promoting DC2, depending on the activation signals. We studied the ability of these effector DC subsets to support HIV-1 transmission in vitro. Compared with iDC, virus transmission is greatly upregulated for the DC1 subset, whereas DC2 cells are inactive. Increased transmission by DC1 correlates with increased expression of ICAM-1, and blocking studies confirm that ICAM-1 expression on DC is important for HIV transmission. The ICAM-1-LFA-1 interaction is known to be important for immunological cross talk between DC and T cells, and our results indicate that this cell-cell contact is exploited by HIV-1 for efficient transmission.


2007 ◽  
Vol 81 (12) ◽  
pp. 6623-6631 ◽  
Author(s):  
Samuel J. Rulli ◽  
Catherine S. Hibbert ◽  
Jane Mirro ◽  
Thoru Pederson ◽  
Shyam Biswal ◽  
...  

ABSTRACT Assembly of retrovirus particles normally entails the selective encapsidation of viral genomic RNA. However, in the absence of packageable viral RNA, assembly is still efficient, and the released virus-like particles (termed “Ψ−” particles) still contain roughly normal amounts of RNA. We have proposed that cellular mRNAs replace the genome in Ψ− particles. We have now analyzed the mRNA content of Ψ− and Ψ+ murine leukemia virus (MLV) particles using both microarray analysis and real-time reverse transcription-PCR. The majority of mRNA species present in the virus-producing cells were also detected in Ψ− particles. Remarkably, nearly all of them were packaged nonselectively; that is, their representation in the particles was simply proportional to their representation in the cells. However, a small number of low-abundance mRNAs were greatly enriched in the particles. In fact, one mRNA species was enriched to the same degree as Ψ+ genomic RNA. Similar results were obtained with particles formed from the human immunodeficiency virus type 1 (HIV-1) Gag protein, and the same mRNAs were enriched in MLV and HIV-1 particles. The levels of individual cellular mRNAs were ∼5- to 10-fold higher in Ψ− than in Ψ+ MLV particles, in agreement with the idea that they are replacing viral RNA in the former. In contrast, signal recognition particle RNA was present at the same level in Ψ− and Ψ+ particles; a minor fraction of this RNA was weakly associated with genomic RNA in Ψ+ MLV particles.


2004 ◽  
Vol 279 (38) ◽  
pp. 39886-39894 ◽  
Author(s):  
Ariel Roldan ◽  
Rodney S. Russell ◽  
Bruno Marchand ◽  
Matthias Götte ◽  
Chen Liang ◽  
...  
Keyword(s):  

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1112 ◽  
Author(s):  
Samy Sid Ahmed ◽  
Nils Bundgaard ◽  
Frederik Graw ◽  
Oliver Fackler

HIV-1 can use cell-free and cell-associated transmission modes to infect new target cells, but how the virus spreads in the infected host remains to be determined. We recently established 3D collagen cultures to study HIV-1 spread in tissue-like environments and applied iterative cycles of experimentation and computation to develop a first in silico model to describe the dynamics of HIV-1 spread in complex tissue. These analyses (i) revealed that 3D collagen environments restrict cell-free HIV-1 infection but promote cell-associated virus transmission and (ii) defined that cell densities in tissue dictate the efficacy of these transmission modes for virus spread. In this review, we discuss, in the context of the current literature, the implications of this study for our understanding of HIV-1 spread in vivo, which aspects of in vivo physiology this integrated experimental–computational analysis takes into account, and how it can be further improved experimentally and in silico.


2000 ◽  
Vol 74 (24) ◽  
pp. 11811-11824 ◽  
Author(s):  
Kalpana Gupta ◽  
David Ott ◽  
Thomas J. Hope ◽  
Robert F. Siliciano ◽  
Jef D. Boeke

ABSTRACT Active nuclear import of the human immunodeficiency virus type 1 (HIV-1) preintegration complex (PIC) is essential for the productive infection of nondividing cells. Nuclear import of the PIC is mediated by the HIV-1 matrix protein, which also plays several critical roles during viral entry and possibly during virion production facilitating the export of Pr55Gag and genomic RNA. Using a yeast two-hybrid screen, we identified a novel human virion-associated matrix-interacting protein (VAN) that is highly conserved in vertebrates and expressed in most human tissues. Its expression is upregulated upon activation of CD4+ T cells. VAN is efficiently incorporated into HIV-1 virions and, like matrix, shuttles between the nucleus and cytoplasm. Furthermore, overexpression of VAN significantly inhibits HIV-1 replication in tissue culture. We propose that VAN regulates matrix nuclear localization and, by extension, both nuclear import of the PIC and export of Pr55Gag and viral genomic RNA during virion production. Our data suggest that this regulatory mechanism reflects a more global process for regulation of nucleocytoplasmic transport.


Scientifica ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-30 ◽  
Author(s):  
Charles R. Rinaldo

Since the 1990s we have known of the fascinating ability of a complex set of professional antigen presenting cells (APCs; dendritic cells, monocytes/macrophages, and B lymphocytes) to mediate HIV-1transinfection of CD4+T cells. This results in a burst of virus replication in the T cells that is much greater than that resulting from direct,cisinfection of either APC or T cells, ortransinfection between T cells. Such APC-to-T celltransinfection first involves a complex set of virus subtype, attachment, entry, and replication patterns that have many similarities among APC, as well as distinct differences related to virus receptors, intracellular trafficking, and productive and nonproductive replication pathways. The end result is that HIV-1 can sequester within the APC for several days and be transmitted via membrane extensions intracellularly and extracellularly to T cells across the virologic synapse. Virus replication requires activated T cells that can develop concurrently with the events of virus transmission. Further research is essential to fill the many gaps in our understanding of thesetransinfection processes and their role in natural HIV-1 infection.


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