Single amino acid change in gp41 region of HIV-1 alters bystander apoptosis and CD4 decline in humanized mice.
BACKGROUND
The mechanism by which HIV infection leads to a selective depletion of CD4 cells leading to immunodeficiency remains highly debated. Whether the loss of CD4 cells is a direct consequence of virus infection or bystander apoptosis of uninfected cells is also uncertain.


RESULTS
We have addressed this issue in the humanized mouse model of HIV infection using a HIV variant with a point mutation in the gp41 region of the Env glycoprotein that alters its fusogenic activity. We demonstrate here that a single amino acid change (V38E) altering the cell-to-cell fusion activity of the Env minimizes CD4 loss in humanized mice without altering viral replication. This differential pathogenesis was associated with a lack of bystander apoptosis induction by V38E virus even in the presence of similar levels of infected cells. Interestingly, immune activation was observed with both WT and V38E infection suggesting that the two phenomena are likely not interdependent in the mouse model.


CONCLUSIONS
We conclude that Env fusion activity is one of the determinants of HIV pathogenesis and it may be possible to attenuate HIV by targeting gp41.
Center of Excellence for Infectious Disease, Department of Biomedical Sciences, Texas Tech University Health Sciences Center, 5001 El Paso Drive, El Paso, Texas 79905, USA. himanshu.garg@ttuhsc.edu
Himanshu
H
Garg
Anjali
A
Joshi
Chunting
C
Ye
Premlata
P
Shankar
N
N
Manjunath
D000818:Animals; D017209:Apoptosis; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism*; D020125:Mutation, Missense; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
D015700:HIV Envelope Protein gp41; D050505:Mutant Proteins; D037521:Virulence Factors; C514787:gp41 protein, Human immunodeficiency virus 1
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