scholarly journals HIV-1 hijacks the cell extracellular matrix to spread collectively and efficiently between T lymphocytes

2021 ◽  
Author(s):  
Catherine Inizan ◽  
Marina Caillet ◽  
Alexandra Desrames ◽  
Perrine Bomme ◽  
Adeline MALLET ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
T Lymphocytes ◽  
Neutralizing Antibodies ◽  
Antiretroviral Treatment ◽  
Broadly Neutralizing Antibodies ◽  
Viral Dissemination ◽  
Viral Spread ◽  
Viral Particles ◽  
Hiv 1

Collective transmission via structures containing several virions has recently emerged as a highly efficient mode of viral spread. Here, we demonstrate that HIV-1 spreads between T lymphocytes in the form of viral particles colonies that are concentrated and sheltered in an extracellular matrix (ECM) lattice enabling their collective transmission upon cell contacts. Intrinsically, ECM-clustered viruses infect T lymphocytes more efficiently than individual viral particles. They preserve HIV-1 transmission from antiretroviral treatment (ArT) and potent broadly neutralizing antibodies. We also show that collagen induced by HIV-1 infection controls the clustering of virions and their collective spread, thereby enhancing infectivity. CD4+ T cells from HIV-1-infected patients produce and transmit ECM-virus clusters, supporting that they could be involved in vivo. This study provides new insights into modes of HIV-1 transmission and identifies a novel fundamental role for collagen in this process. HIV-1 spread via ECM-virus clusters may have important implications for viral dissemination and persistence, including during therapy.

scholarly journals Effect of HIV-1 Env on SERINC5 Antagonism

2016 ◽  
Vol 91 (4) ◽  
Author(s):  
Saina Beitari ◽  
Shilei Ding ◽  
Qinghua Pan ◽  
Andrés Finzi ◽  
Chen Liang
Keyword(s):  
Antiviral Activity ◽  
High Frequency ◽  
Neutralizing Antibodies ◽  
Broadly Neutralizing Antibodies ◽  
Viral Loads ◽  
Virion Incorporation ◽  
Viral Particles ◽  
Ccr5 Inhibitor ◽  
Hiv 1

ABSTRACT SERINC5 is able to restrict HIV-1 infection by drastically impairing the infectivity of viral particles. Studies have shown that the HIV-1 Nef protein counters SERINC5 through downregulating SERINC5 from the cell surface and preventing the virion incorporation of SERINC5. In addition, the Env proteins of some HIV-1 strains can also overcome SERINC5 inhibition. However, it is unclear how HIV-1 Env does so and why HIV-1 has two mechanisms to resist SERINC5 inhibition. The results of this study show that neither Env nor Nef prevents high levels of ectopic SERINC5 from being incorporated into HIV-1 particles, except that Env, but not Nef, is able to resist inhibition by virion-associated SERINC5. Testing of a panel of HIV-1 Env proteins from different subtypes revealed a high frequency of SERINC5-resistant Envs. Interestingly, although the SERINC5-bearing viruses were not inhibited by SERINC5 itself, they became more sensitive to the CCR5 inhibitor maraviroc and some neutralizing antibodies than the SERINC5-free viruses, which suggests a possible influence of SERINC5 on Env function. We conclude that HIV-1 Env is able to overcome SERINC5 without preventing SERINC5 virion incorporation. IMPORTANCE HIV-1 Nef is known to enhance the infectivity of HIV-1 particles and to contribute to the maintenance of high viral loads in patients. However, the underlying molecular mechanism remained elusive until the recent discovery of the antiviral activity of SERINC5. SERINC5 profoundly inhibits HIV-1 but is antagonized by Nef, which prevents the incorporation of SERINC5 into viral particles. Here, we show that HIV-1 Env, but not Nef, is able to resist high levels of SERINC5 without excluding SERINC5 from incorporation into viral particles. However, the virion-associated SERINC5 renders HIV-1 more sensitive to some broadly neutralizing antibodies. It is possible that, under the pressure of some neutralizing antibodies in vivo, HIV-1 needs Nef to remove SERINC5 from viral particles, even though viral Env is able to resist virion-associated SERINC5.

scholarly journals New Connections: Cell-to-Cell HIV-1 Transmission, Resistance to Broadly Neutralizing Antibodies, and an Envelope Sorting Motif

2017 ◽  
Vol 91 (9) ◽  
Author(s):  
S. Abigail Smith ◽  
Cynthia A. Derdeyn
Keyword(s):  
Neutralizing Antibodies ◽  
Differential Susceptibility ◽  
Neutralizing Antibody ◽  
Dependent Manner ◽  
Broadly Neutralizing Antibodies ◽  
Cell Infection ◽  
Viral Spread ◽  
Broadly Neutralizing Antibody ◽  
Hiv 1

ABSTRACT HIV-1 infection from cell-to-cell may provide an efficient mode of viral spread in vivo and could therefore present a significant challenge for preventative or therapeutic strategies based on broadly neutralizing antibodies. Indeed, Li et al. (H. Li, C. Zony, P. Chen, and B. K. Chen, J. Virol. 91:e02425-16, 2017, https://doi.org/10.1128/JVI.02425-16 ) showed that the potency and magnitude of multiple HIV-1 broadly neutralizing antibody classes are decreased during cell-to-cell infection in a context-dependent manner. A functional motif in gp41 appears to contribute to this differential susceptibility by modulating exposure of neutralization epitopes.

scholarly journals Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo

Science ◽  
2016 ◽  
Vol 352 (6288) ◽  
pp. 1001-1004 ◽  
Author(s):  
C.-L. Lu ◽  
D. K. Murakowski ◽  
S. Bournazos ◽  
T. Schoofs ◽  
D. Sarkar ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Broadly Neutralizing Antibodies ◽  
Infected Cells ◽  
Hiv 1

Expression of HIV-1 broadly neutralizing antibodies mediated by recombinant adeno-associated virus 8 in vitro and in vivo

2016 ◽  
Vol 80 ◽  
pp. 68-77
Author(s):  
Yongjiao Yu ◽  
Lu Fu ◽  
Xiaoyu Jiang ◽  
Shanshan Guan ◽  
Ziyu Kuai ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Broadly Neutralizing Antibodies ◽  
Adeno Associated Virus ◽  
Hiv 1

scholarly journals Broadly neutralizing antibodies that inhibit HIV-1 cell to cell transmission

2013 ◽  
Vol 210 (13) ◽  
pp. 2813-2821 ◽  
Author(s):  
Marine Malbec ◽  
Françoise Porrot ◽  
Rejane Rua ◽  
Joshua Horwitz ◽  
Florian Klein ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Target Cells ◽  
Type I ◽  
Broadly Neutralizing Antibodies ◽  
Major Mechanism ◽  
Viral Spread ◽  
Cell Transmission ◽  
Cd4 Binding Site ◽  
Virological Synapses ◽  
Hiv 1

The neutralizing activity of anti–HIV-1 antibodies is typically measured in assays where cell-free virions enter reporter cell lines. However, HIV-1 cell to cell transmission is a major mechanism of viral spread, and the effect of the recently described broadly neutralizing antibodies (bNAbs) on this mode of transmission remains unknown. Here we identify a subset of bNAbs that inhibit both cell-free and cell-mediated infection in primary CD4+ lymphocytes. These antibodies target either the CD4-binding site (NIH45-46 and 3BNC60) or the glycan/V3 loop (10-1074 and PGT121) on HIV-1 gp120 and act at low concentrations by inhibiting multiple steps of viral cell to cell transmission. These antibodies accumulate at virological synapses and impair the clustering and fusion of infected and target cells and the transfer of viral material to uninfected T cells. In addition, they block viral cell to cell transmission to plasmacytoid DCs and thereby interfere with type-I IFN production. Thus, only a subset of bNAbs can efficiently prevent HIV-1 cell to cell transmission, and this property should be considered an important characteristic defining antibody potency for therapeutic or prophylactic antiviral strategies.

scholarly journals Neutralizing antibodies inhibit HIV-1 transfer from primary dendritic cells to autologous CD4 T lymphocytes

Blood ◽  
2012 ◽  
Vol 120 (18) ◽  
pp. 3708-3717 ◽  
Author(s):  
Bin Su ◽  
Ke Xu ◽  
Alexandre Lederle ◽  
Maryse Peressin ◽  
Marina Elizabeth Biedma ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Lymphocytes ◽  
Neutralizing Antibodies ◽  
Sexual Transmission ◽  
Viral Particles ◽  
In Trans ◽  
In Cis ◽  
Kinetics Of ◽  
Hiv 1 ◽  
Dc Maturation

AbstractDendritic cells (DCs) support only low levels of HIV-1 replication, but have been shown to transfer infectious viral particles highly efficiently to neighboring permissive CD4 T lymphocytes. This mode of cell-to-cell HIV-1 spread may be a predominant mode of infection and dissemination. In the present study, we analyzed the kinetics of fusion, replication, and the ability of HIV-1–specific Abs to inhibit HIV-1 transfer from immature DCs to autologous CD4 T lymphocytes. We found that neutralizing mAbs prevented HIV-1 transfer to CD4 T lymphocytes in trans and in cis, whereas nonneutralizing Abs did not. Neutralizing Abs also significantly decreased HIV-1 replication in DCs, even when added 2 hours after HIV-1 infection. Interestingly, a similar inhibition of HIV-1 replication in DCs was detected with some nonneutralizing Abs and was correlated with DC maturation. We suggest that the binding of HIV-1-specific Abs to FcγRs leads to HIV-1 inhibition in DCs by triggering DC maturation. This efficient inhibition of HIV-1 transfer by Abs highlights the importance of inducing HIV-specific Abs by vaccination directly at the mucosal portal of HIV-1 entry to prevent early dissemination after sexual transmission.

A recombinant live attenuated measles vaccine vector primes effective HLA-A0201-restricted cytotoxic T lymphocytes and broadly neutralizing antibodies against HIV-1 conserved epitopes

Vaccine ◽  
2005 ◽  
Vol 23 (36) ◽  
pp. 4463-4472 ◽  
Author(s):  
Clarisse Lorin ◽  
Frédéric Delebecque ◽  
Valérie Labrousse ◽  
Lucie Da Silva ◽  
François Lemonnier ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Neutralizing Antibodies ◽  
Vaccine Vector ◽  
Measles Vaccine ◽  
Broadly Neutralizing Antibodies ◽  
Hiv 1

scholarly journals Predicting in vivo escape dynamics of HIV-1 from a broadly neutralizing antibody

2021 ◽  
Vol 118 (30) ◽  
pp. e2104651118
Author(s):  
Matthijs Meijers ◽  
Kanika Vanshylla ◽  
Henning Gruell ◽  
Florian Klein ◽  
Michael Lässig
Keyword(s):  
Viral Load ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Broadly Neutralizing Antibodies ◽  
Antibody Treatment ◽  
Trade Off ◽  
Escape Dynamics ◽  
Resistance Evolution ◽  
Hiv 1

Broadly neutralizing antibodies are promising candidates for treatment and prevention of HIV-1 infections. Such antibodies can temporarily suppress viral load in infected individuals; however, the virus often rebounds by escape mutants that have evolved resistance. In this paper, we map a fitness model of HIV-1 interacting with broadly neutralizing antibodies using in vivo data from a recent clinical trial. We identify two fitness factors, antibody dosage and viral load, that determine viral reproduction rates reproducibly across different hosts. The model successfully predicts the escape dynamics of HIV-1 in the course of an antibody treatment, including a characteristic frequency turnover between sensitive and resistant strains. This turnover is governed by a dosage-dependent fitness ranking, resulting from an evolutionary trade-off between antibody resistance and its collateral cost in drug-free growth. Our analysis suggests resistance–cost trade-off curves as a measure of antibody performance in the presence of resistance evolution.

scholarly journals Different In Vivo Effects of HIV-1 Immunodominant Epitope-Specific Cytotoxic T Lymphocytes on Selection of Escape Mutant Viruses

2010 ◽  
Vol 84 (11) ◽  
pp. 5508-5519 ◽  
Author(s):  
Hirokazu Koizumi ◽  
Masao Hashimoto ◽  
Mamoru Fujiwara ◽  
Hayato Murakoshi ◽  
Takayuki Chikata ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Neutralizing Antibodies ◽  
Escape Mutant ◽  
Escape Mutants ◽  
Hiv 1 ◽  
Selection Of ◽  
Strong Ability

ABSTRACT HIV-1 escape mutants are well known to be selected by immune pressure via HIV-1-specific cytotoxic T lymphocytes (CTLs) and neutralizing antibodies. The ability of the CTLs to suppress HIV-1 replication is assumed to be associated with the selection of escape mutants from the CTLs. Therefore, we first investigated the correlation between the ability of HLA-A*1101-restricted CTLs recognizing immunodominant epitopes in vitro and the selection of escape mutants. The result showed that there was no correlation between the ability of these CTLs to suppress HIV-1 replication in vitro and the appearance of escape mutants. The CTLs that had a strong ability to suppress HIV-1 replication in vitro but failed to select escape mutants expressed a higher level of PD-1 in vivo, whereas those that had a strong ability to suppress HIV-1 replication in vitro and selected escape mutants expressed a low level of PD-1. Ex vivo analysis of these CTLs revealed that the latter CTLs had a significantly stronger ability to recognize the epitope than the former ones. These results suggest that escape mutations are selected by HIV-1-specific CTLs that have a stronger ability to recognize HIV-1 in vivo but not in vitro.

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