Breakthrough in Virology

Look here for the latest groundbreaking findings in virology research:

Coeliac disease (CD) is a unique immune disease characterized by a T-cell immune response against wheat associated gluten in patients expressing the HLA DQ2 or DQ8 alleles. In CD, the usual immunologic tolerance towards dietary antigens is broken, causing intestinal villous atrophy and protean clinical consequences ranging from malabsorption to intestinal lymphoma. It has been long hypothesised that infectious agents may trigger an immune response towards gluten in genetically predisposed individuals. However, most studies on this topic rely on epidemiological data as it proved difficult to establish a solid experimental model to study the interaction between single infectious agents and onset of CD. In BOUZIAT, Romain, et al. Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease. Science, 2017, 356.6333: 44-50. , a very interesting model involving the human T1L and T3D isolates of the dsRNA reovirus and mice was developed. Both strains do not cause intestinal damage, but T1L is able to infect intestinal epithelial cells and elicit an immune response, while the T3D is not. A reassortant T3D (T3D-RV) harbouring the S1 and L2 genetic segments of T1L was produced. T3D-RV proved able to infect the intestine and generate a protective immune response. Nevertheless, when the authors of the study performed a non-biased gene expression profiling assay on lamina propria (Lp) and mesenteric lymphnodes (mLN) tissues, they discovered that especially after 48 hours T1L caused a markedly higher expression of genes involved in immune and inflammatory pathways such as IFN-I signaling. Furthermore, T1L induced a proinflammatory phenotype in a subset of mLN dendritic cells which takes up most dietary ovalbumin. In vivo, T1L also inhibited the conversion of ovalbumin specific CD4+ T cells into regulatory T cells (Tregs) promoting their differentiation into proinflammatory Th1-like cells. Eventually, the authors studied the effect of T1L infection in CD-predisposed transgenic DQ8tg mice, which lost oral tolerance to gluten, with the induction of anti-gliadin antibodies and a cutaneous Th1 hypersensitivity reaction to gluten. This animal model provides mechanistic insights into the role of viruses in the pathogenesis of coeliac disease, through modulation of the host immune response.

Alberto Reale, MD, Department of Molecular Medicine, University of Padova, Italy

Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen.

Xu M, Lee EM, Wen Z, Cheng Y, Huang WK, Qian X, Tcw J, Kouznetsova J, Ogden SC, Hammack C, Jacob F, Nguyen HN, Itkin M, Hanna C, Shinn P, Allen C, Michael SG, Simeonov A, Huang W, Christian KM, Goate A, Brennand KJ, Huang R, Xia M, Ming GL, Zheng W, Song H, Tang H.

Nat Med. 2016 Aug 29. doi: 10.1038/nm.4184

A Screen of FDA-Approved Drugs for Inhibitors of Zika Virus Infection.

Barrows NJ, Campos RK, Powell ST, Prasanth KR, Schott-Lerner G, Soto-Acosta R, Galarza-Muñoz G, McGrath EL, Urrabaz-Garza R, Gao J, Wu P, Menon R, Saade G, Fernandez-Salas I, Rossi SL, Vasilakis N, Routh A, Bradrick SS, Garcia-Blanco MA.

Cell Host Microbe. 2016 Aug 10;20(2):259-70. doi: 10.1016/j.chom.2016.07.004. Epub 2016 Jul 28.

A CRISPR screen defines a signal peptide processing pathway required by flaviviruses.

Zhang R, Miner JJ, Gorman MJ, Rausch K, Ramage H, White JP, Zuiani A, Zhang P, Fernandez E, Zhang Q, Dowd KA, Pierson TC, Cherry S, Diamond MS.

Nature. 2016 Jul 7;535(7610):164-8.

Zika Virus Associated with Microcephaly.

Mlakar J, Korva M, Tul N, Popović M, Poljšak-Prijatelj M, Mraz J, Kolenc M, Resman Rus K, Vesnaver Vipotnik T, Fabjan Vodušek V, Vizjak A, Pižem J, Petrovec M, Avšič Županc T.

N Engl J Med. 2016 Feb 10. [Epub ahead of print]

AAV-expressed eCD4-Ig provides durable protection from multiple SHIV challenges.

Gardner MR, Kattenhorn LM, Kondur HR, von Schaewen M, Dorfman T, Chiang JJ, Haworth KG, Decker JM, Alpert MD, Bailey CC, Neale ES, Fellinger CH, Joshi VR, Fuchs SP, Martinez-Navio JM, Quinlan BD, Yao AY, Mouquet H, Gorman J, Zhang B, Poignard P, Nussenzweig MC, Burton DR, Kwong PD9, Piatak M, Lifson JD, Gao G, Desrosiers RC, Evans DT, Hahn BH, Ploss A, Cannon PM, Seaman MS, Farzan M.

Nature. 2015 Feb 18. doi:10.1038/nature14264.

Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430.

Warren TK, Wells J, Panchal RG, Stuthman KS, Garza NL, Van Tongeren SA, Dong L, Retterer CJ, Eaton BP, Pegoraro G, Honnold S, Bantia S, Kotian P, Chen X, Taubenheim BR, Welch LS, Minning DM, Babu YS, Sheridan WP, Bavari S.

Nature. 2014 Apr 17. doi: 10.1038/nature13027.

Flavivirus NS1 structures reveal surfaces for associations with membranes and the immune system.

Akey DL, Brown WC, Dutta S, Konwerski J, Jose J, Jurkiw TJ, DelProposto J, Ogata CM, Skiniotis G, Kuhn RJ, Smith JL.

Science. 2014 Feb 21;343(6173):881-5. doi: 10.1126/science.1247749.

Structure of the CCR5 chemokine receptor-HIV entry inhibitor maraviroc complex.

Tan Q, Zhu Y, Li J, Chen Z, Han GW, Kufareva I, Li T, Ma L, Fenalti G, Li J, Zhang W, Xie X, Yang H, Jiang H, Cherezov V, Liu H, Stevens RC, Zhao Q, Wu B.

Science. 2013 Sep 20;341(6152):1387-90. doi: 10.1126/science.1241475.

Press release from the Scripps research institute.

Immune clearance of highly pathogenic SIV infection.

Hansen SG, Jr MP, Ventura AB, Hughes CM, Gilbride RM, Ford JC, Oswald K, Shoemaker R, Li Y, Lewis MS, Gilliam AN, Xu G, Whizin N, Burwitz BJ, Planer SL, Turner JM, Legasse AW, Axthelm MK, Nelson JA, Früh K, Sacha JB, Estes JD, Keele BF, Edlefsen PT, Lifson JD, Picker LJ.

Nature. 2013 Sep 11. doi: 10.1038/nature12519.

Human MX2 is an interferon-induced post-entry inhibitor of HIV-1 infection.

Goujon C, Moncorgé O, Bauby H, Doyle T, Ward CC, Schaller T, Hué S, Barclay WS, Schulz R, Malim MH.

Nature. 2013 Sep 18. doi: 10.1038/nature12542.

MX2 is an interferon-induced inhibitor of HIV-1 infection.

Kane M, Yadav SS, Bitzegeio J, Kutluay SB, Zang T, Wilson SJ, Schoggins JW, Rice CM, Yamashita M, Hatziioannou T, Bieniasz PD.

Nature. 2013 Oct 24. doi: 10.1038/nature12653.

The Interferon-Inducible MxB Protein Inhibits HIV-1 Infection.

Liu Z, Pan Q, Ding S, Qian J, Xu F, Zhou J, Cen S, Guo F, Liang C.

Cell Host Microbe. 2013 Oct 16. doi: 10.1016/j.chom.2013.08.015.

Referred to by Otto Haller: Dynamins Are Forever: MxB Inhibits HIV-1

Cell Host Microbe. 2013 Oct 16. doi: 10.1016/j.chom.2013.10.002.