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Published on: September 1, 2015
Pandemic HIV-1 Vpu overcomes intrinsic herd immunity mediated by tetherin
Shingo Iwami1, Kei Sato2, Satoru Morita3
11] Mathematical Biology Laboratory, Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka, Fukuoka 8128581, Japan [2] PRESTO, JST, Kawaguchi, Saitama 3320012, Japan [3] CREST, JST, Kawaguchi, Saitama 3320012, Japan.
Abstract:
Among the four groups of HIV-1 (M, N, O, and P), HIV-1M alone is pandemic and has rapidly expanded across the world. However, why HIV-1M has caused a devastating pandemic while the other groups remain contained is unclear. Interestingly, only HIV-1M Vpu, a viral protein, can robustly counteract human tetherin, which tethers budding virions. Therefore, we hypothesize that this property of HIV-1M Vpu facilitates human-to-human viral transmission. Adopting a multilayered experimental-mathematical approach, we demonstrate that HIV-1M Vpu confers a 2.38-fold increase in the prevalence of HIV-1 transmission. When Vpu activity is lost, protected human populations emerge (i.e., intrinsic herd immunity develops) through the anti-viral effect of tetherin. We also reveal that all Vpus of transmitted/founder HIV-1M viruses maintain anti-tetherin activity. These findings indicate that tetherin plays the role of a host restriction factor, providing 'intrinsic herd immunity', whereas Vpu has evolved in HIV-1M as a tetherin antagonist.
Insights
The HIV-1M Vpu protein enhances human-to-human HIV transmission by counteracting tetherin. Loss of Vpu activity allows tetherin to provide herd immunity against the virus.
Area of Science:
- Virology
- Immunology
- Epidemiology
Background:
- HIV-1 group M is pandemic, unlike groups N, O, and P.
- The Vpu protein of HIV-1M uniquely counteracts human tetherin, a factor that restricts viral release.
- The mechanism behind HIV-1M's pandemic spread while other groups remain contained is not fully understood.
Purpose of the Study:
- To investigate the role of HIV-1M Vpu in viral transmission.
- To test the hypothesis that Vpu's ability to counteract tetherin facilitates human-to-human transmission.
- To explore the implications of tetherin as a host restriction factor.
Main Methods:
- Utilized a multilayered experimental-mathematical approach.
- Assessed the impact of Vpu activity on HIV-1 transmission rates.
- Analyzed Vpu sequences from transmitted/founder HIV-1M viruses.
Main Results:
- HIV-1M Vpu confers a 2.38-fold increase in HIV-1 transmission prevalence.
- Loss of Vpu activity leads to the emergence of protected human populations due to tetherin's antiviral effect, establishing intrinsic herd immunity.
- All Vpu proteins from transmitted/founder HIV-1M viruses exhibit anti-tetherin activity.
Conclusions:
- HIV-1 Vpu is a key factor driving the pandemic spread of HIV-1M.
- Tetherin acts as a host restriction factor, conferring intrinsic herd immunity against HIV-1.
- Vpu has evolved in HIV-1M specifically as a potent antagonist of tetherin, enabling viral propagation.
