Cell Rep: Uncovering a novel mechanism by which HIV-1 evades attack by the host body's immune system

Recently, a study entitled "HIV-1 Vpu restricts Fc-mediated effector functions in vivo" published in the international journal Cell Reports, scientists from the University of Montreal and other institutions found that the types of viruses used to study the efficacy of non-neutralizing antibodies against HIV may play a key role
。 In the paper, the researchers found for the first time through studies of humanized mice that the expression of the viral protein Vpu is essential
for promoting the elimination of the body's antibody dependent cell-mediated cytotoxicity (ADCC) by infected cells.

This mechanism has been well documented in the scientific literature and can be used by non-neutralizing antibodies to get rid of cells infected by viruses; In order to develop a new vaccine that can protect against HIV-1, many laboratories around the world have developed the same type of antibodies to prevent HIV infection
.
Today, millions of people around the world are infected with HIV-1 and have non-neutralizing antibodies in their bodies, but the disease has not been effectively eliminated, and if these antibodies become effective, why is it not working properly?

Researcher Finzi said that we observed that HIV-1 modified in some laboratory experiments does not express Vpu, however, in naturally occurring viruses, the protein actually acts as a bodyguard in infected cells, allowing self-replication and better protecting itself
by evading surveillance by the host body's immune system.
In fact, the researchers found that by expressing Vpu in infected cells, non-neutralizing antibodies may have difficulty recognizing these cells in the body, so these cells choose to avoid the ADCC response
.

Revealing a new mechanism
by which HIV-1 evades attack by the host body's immune system.

Image source: Cell Reports (2022).
DOI:10.
1016/j.
celrep.
2022.
111624

The researchers subsequently confirmed this observation by studying humanized mice receiving non-neutralizing antibodies, and compared to animals infected with naturally occurring viruses, a decrease in viral load was observed in animals infected only by viruses that did not express Vpu, an observation that corroborated
previous studies by the researchers 。 As early as 2013, researchers Andrés Finzi and others found that infected cells can be protected from ADCC responses because the envelope of the virus remains closed under the action of Vpu and the protein Nef (the second bodyguard), and in the case of complete blocking, infected cells will not be detected
by nearby antibodies.

The researchers say that in the laboratory, if Vpu is not expressed in the virus used, the outer membrane of infected cells will open up, and if it is not protected, it will be attacked by antibodies, which may well explain some surprising results from research with non-neutralizing antibodies, and in real life, HIV is always on alert due to the presence of two bodyguard proteins
, Vpu and Nef 。 According to WHO data, as of the end of 2021, more than 38 million people worldwide had HIV-caused AIDS, and the researchers believe that the results of this study may provide valuable information for future researchers to develop new vaccines against HIV-1 and new strategies
to clear the body of the virus.
In summary, the results of this study highlight the importance of Vpuprotein-mediated evasion of
humoral responses.
(Biovalley Bioon.
com)

Original source:

Jérémie Prévost，Sai Priya Anand，Jyothi Krishnaswamy Rajashekar，et al.
 HIV-1 Vpu restricts Fc-mediated effector functions in vivo, Cell Reports (2022).
DOI:10.
1016/j.
celrep.
2022.
111624