Tracing HIV-1 transmission: envelope traits of HIV-1 transmitter and recipient pairs.
Mucosal HIV-1 transmission predominantly results in a single transmitted/founder (T/F) virus establishing infection in the new host despite the generally high genetic diversity of the transmitter virus population. To what extent HIV-1 transmission is a stochastic process or driven by selective forces that allow T/F viruses best to overcome bottlenecks in transmission has not been conclusively resolved. Building on prior investigations that suggest HIV-1 envelope (Env) features to contribute in the selection process during transmission, we compared phenotypic virus characteristics of nine HIV-1 subtype B transmission pairs, six men who have sex with men and three male-to-female transmission pairs.



All recipients were identified early in acute infection and harbored based on extensive sequencing analysis a single T/F virus allowing a controlled analysis of virus properties in matched transmission pairs. Recipient and transmitter viruses from the closest time point to transmission showed no signs of selection for specific Env modifications such as variable loop length and glycosylation. Recipient viruses were resistant to circulating plasma antibodies of the transmitter and also showed no altered sensitivity to a large panel of entry inhibitors and neutralizing antibodies. The recipient virus did not consistently differ from the transmitter virus in terms of entry kinetics, cell-cell transmission and replicative capacity in primary cells. Our paired analysis revealed a higher sensitivity of several recipient virus isolates to interferon-α (IFNα) which suggests that resistance to IFNα cannot be a general driving force in T/F establishment.



With the exception of increased IFNα sensitivity, none of the phenotypic virus properties we investigated clearly distinguished T/F viruses from their matched transmitter viruses supporting the notion that at least in subtype B infection HIV-1 transmission is to a considerable extent stochastic.
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.|Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
Corinna S
CS
Oberle
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.|Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
Beda
B
Joos
Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
Peter
P
Rusert
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.|Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
Nottania K
NK
Campbell
Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
David
D
Beauparlant
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.|Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
Herbert
H
Kuster
Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
Jacqueline
J
Weber
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.|Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
Corinne D
CD
Schenkel
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.|Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
Alexandra U
AU
Scherrer
Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
Carsten
C
Magnus
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.|Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
Roger
R
Kouyos
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Philip
P
Rieder
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Barbara
B
Niederöst
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Dominique L
DL
Braun
Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
Jovan
J
Pavlovic
Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
Jürg
J
Böni
Laboratory of Virology, University Hospital Geneva, University of Geneva, Geneva, Switzerland.
Sabine
S
Yerly
Department of Biomedicine, University of Basel, Basel, Switzerland.
Thomas
T
Klimkait
Division of Immunology and Allergy, University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland.
Vincent
V
Aubert
Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
Alexandra
A
Trkola
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.|Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
Karin J
KJ
Metzner
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. huldrych.guenthard@usz.ch.|Institute of Medical Virology, University of Zurich, Zurich, Switzerland. huldrych.guenthard@usz.ch.
Huldrych F
HF
Günthard
D000208:Acute Disease; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D005260:Female; D014644:Genetic Variation; D015658:HIV Infections / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology*; D018451:Homosexuality, Male; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D008297:Male; D009500:Neutralization Tests; D010641:Phenotype; D017422:Sequence Analysis, DNA; D013269:Stochastic Processes; D056189:Viral Tropism; D053586:Virus Internalization; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology
D057134:Antibodies, Neutralizing; D016898:Interferon-alpha; D054299:env Gene Products, Human Immunodeficiency Virus
Entry; Envelope; HIV-1; IFNα; Neutralization; Replicative capacity; Transmission