Cell Reports article explains how HIV-1 evades the immune system

According to the World Health Organization, more than 38 million people worldwide were infected with the human immunodeficiency virus (HIV-1)
by the end of 2021.
This is a retrovirus that causes immune deficiencies in human cells, leading to various opportunistic infections and tumorigenesis
.

To develop a vaccine against HIV-1, many labs are studying how to produce antibodies
.
Given the difficulty of eliciting broad-spectrum neutralizing antibodies in vivo, non-neutralizing antibodies (nnAbs) are an alternative
.
Non-neutralizing antibodies represent most antibodies in the plasma of HIV-1 infected people and are easily triggered
by vaccination.

Today, millions of people living with HIV-1 carry non-neutralizing antibodies
.
Despite this, the disease remains difficult to eradicate
.
If antibodies are so effective, then why do they seem to not work?

A new study led by the University of Montreal in Canada shows for the first time that in humanized mice, the expression of the viral protein Vpu is critical
for infected cells to evade the ADCC clearance mechanism.
ADCC (antibody-dependent cell-mediated cytotoxic effects) is a common mechanism
for non-neutralizing antibodies to clear virus-infected cells.
The results were recently published in the journal Cell Reports
.

Co-corresponding author Professor Andrés Finzi of the University of Montreal said: "We observed that the modified HIV-1 virus used in some laboratories does not express Vpu
.
However, in naturally occurring viruses, Vpu, a protein, actually plays a role
in protecting infected cells.
Once expressed, it replicates itself and protects itself
by dodging the immune system's radar.
”

In fact, studies have shown that if virus-infected cells express Vpuprotein, it is much more difficult for non-neutralizing antibodies to recognize these cells in the body
.
These cells evade the ADCC response
.

Their collaborator, Priti Kumar of Yale School of Medicine, confirmed this observation by conducting experiments on humanized mice receiving non-neutralizing antibodies
.
Compared to wild-type viruses, the viral load decreases
only when mice are infected by Vpu-deficient viruses.

This observation echoes the
team's previous work.
In 2013, a team led by Andrés Finzi demonstrated that infected cells are not affected by the ADCC response because the viral envelope remains closed under the influence of Vpu and Nef proteins
.
Due to complete closure, infected cells cannot be detected
by nearby antibodies.

"In the lab, if you use a virus that doesn't express Vpu, the envelope of the infected cell opens," Finzi says
.
"Without protection, it will be attacked
by antibodies.
This may explain some of the surprising results
in non-neutralizing antibody studies.
In real life, HIV is always on alert thanks to the presence of two bodyguards, Vpu and Nef
.
”

The research team believes that this study provides valuable information
for future HIV-1 vaccine development and virus eradication.

Original search

HIV-1 Vpu restricts Fc-mediated effector functions in vivo