Kinetics of the establishment of HIV-1 viral interference and comprehensive analysis of the contribution of viral genes.
Viral interference defines the reduced susceptibility of an infected cell to reinfection. For HIV-1, both receptor-dependent and independent pathways were described. The relative importance of different receptor-independent pathways has not been addressed. We have used reporter viruses to quantify the percentage of single- and double-infected cells, as a function of the delay between the two infections. For co-infection experiments, the frequency of double infected cells was higher than expected for independent events. By delaying the second infection, this frequency progressively diminished, resulting in significant interference after 18h. Interference measured here was largely receptor-independent. By individually deleting viral genes or expressing them in isolation, we demonstrate that the viral protein Rev plays a dominant role, while other viral proteins contributes to optimal interference. Our study defines the kinetics of early HIV-1 interference, describing the transition from higher susceptibility to double-infection to viral interference, and identifies Rev as its dominant effector.
INSERM, U941, Paris, France; Univ Paris Diderot, Sorbonne Paris Cité, Paris, France; Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France.
Azaria
A
Remion
Univ Paris Diderot, Sorbonne Paris Cité, Paris, France; Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France.
Marc
M
Delord
INSERM, U941, Paris, France; Univ Paris Diderot, Sorbonne Paris Cité, Paris, France; Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France.
Allan J
AJ
Hance
INSERM, U941, Paris, France; Univ Paris Diderot, Sorbonne Paris Cité, Paris, France; Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France.
Sentob
S
Saragosti
INSERM, U941, Paris, France; Univ Paris Diderot, Sorbonne Paris Cité, Paris, France; Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France. Electronic address: fabrizio.mammano@inserm.fr.
Fabrizio
F
Mammano
D002460:Cell Line; D060085:Coinfection / Q000235:genetics / Q000821:virology; D057809:HEK293 Cells; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D012367:RNA, Viral / Q000235:genetics; D011991:Receptors, Virus / Q000235:genetics; D015163:Superinfection / Q000235:genetics* / Q000821:virology; D014762:Viral Interference / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
D012367:RNA, Viral; D011991:Receptors, Virus; D054321:rev Gene Products, Human Immunodeficiency Virus; C514860:rev protein, Human Immunodeficiency Virus-1
HIV-1; Super-infection; Viral interference