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HIV Biological Variability

HIV-1 biological phenotype, such as replication rate and cytopathology in culture, has long been recognised as marker for viral virulence. HIV biological variability, a concept we introduced in the 1980s, has come into focus 10 years later with the discovery of HIV co-receptor use allowing translation of phenotypic traits into molecular terms. Our work established that primary HIV-1 isolates can be distinguished according to the chemokine receptor used, principally CCR5 or CXCR4, which together with CD4 allow viral entry into cells. HIV-1 isolates obtained from asymptomatic adults or children generally use the CCR5 co-receptor. During disease progression evolution to more flexible use of CCR5 occurs and in a majority of cases there is a shift to CXCR4 use. Early acquisition of CXCR4 use is predictive of a poor prognosis.

The research group in the late 1980s

From left: Jan Albert, Agneta von Gegerfelt and Francesca Chiodi, PhD students, Birgitta Lind, research assistant. Jan Albert and Francesca Chiodi are now professors at the Karolinska Institute, Stockholm.

Left: PhD students Stefan Schwartz and Francesca Chiodi, now professors at Lund University, Lund and the Karolinska Institute, Stockholm, respectively. Right: Assistant Professor Birgitta Åsjö at the State Bacteriological Laboratory. Professor at the University of Bergen, Norway since 1992. The horse was a donor of normal horse serum for the State Bacteriological Laboratory.

The research group in the late 1990s

Left: Yu Shi, Dalma Vödrös and Åsa Björndal, PhD students, Anneka Ehrnst, Associate Professor, and Kerstin Andreasson, research assistant. Right: Robert Fredriksson, research assistant, and Yu Shi and Åsa Björndal, PhD students.

The research group in 2005

From left: Sisay Alamayehu Abayneh, guest researcher, Salma Nowroozalizadeh, Ingrid Karlsson and Johanna Repits, PhD students, Elzbieta Vincic, research assistant, Eva Maria Fenyö, group leader, Mattias Mild, PhD student, Monica Öberg, research assistant, Marianne Jansson, Assistant Professor, Carlotta Kuylenstierna, student, Anna Laurén, PhD student.

List of 13 key publications:

1: Asjö B, Morfeldt-Månson L, Albert J, Biberfeld G, Karlsson A, Lidman K, Fenyö EM. Replicative capacity of human immunodeficiency virus from patients with varying severity of HIV infection. Lancet. 1986 Sep 20;2(8508):660-2. PubMed PMID: 2429124.

2: Fenyö EM, Morfeldt-Månson L, Chiodi F, Lind B, von Gegerfelt A, Albert J, Olausson E, Asjö B. Distinct replicative and cytopathic characteristics of human immunodeficiency virus isolates. J Virol. 1988 Nov;62(11):4414-9. PMID: 2459416.

3: Albert J, Böttiger B, Biberfeld G, Fenyö EM. Replicative and cytopathic characteristics of HIV-2 and severity of infection. Lancet. 1989 Apr 15;1(8642):852-3. PubMed PMID: 2564945.

4: Schwartz S, Felber BK, Fenyö EM, Pavlakis GN. Rapidly and slowly replicating human immunodeficiency virus type 1 isolates can be distinguished according to target-cell tropism in T-cell and monocyte cell lines. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7200-3. PMID: 2789383.

5: Åsjö B, Sharma UK, Morfeldt-Månson L, Magnusson A, Barkhem T, Albert J, Olausson E, von Gegerfelt A, Lind B, Biberfeld P and Fenyö EM. Naturally occurring HIV-1 isolates with differences in replicative capacity are distinguished by in situ hybridization of infected cells. AIDS Res Hum Retroviruses. 1990 Oct;6(10):1177-82. PubMed PMID: 2252637.

6: Fredriksson R, Stålhanske P, von Gegerfelt A, Lind B, Aman P, Rassart E, Fenyö EM. Biological characterization of infectious molecular clones derived from a human immunodeficiency virus type-1 isolate with rapid/high replicative capacity. Virology. 1991 Mar;181(1):55-61. PubMed PMID: 1704660.

7: Björndal A, Deng H, Jansson M, Fiore JR, Colognesi C, Karlsson A, Albert J, Scarlatti G, Littman DR, Fenyö EM. Coreceptor usage of primary human immunodeficiency virus type 1 isolates varies according to biological phenotype. J Virol. 1997 Oct;71(10):7478-87. PMID: 9311827.

8: Berger EA, Doms RW, Fenyö EM, Korber BT, Littman DR, Moore JP, Sattentau QJ, Schuitemaker H, Sodroski J, Weiss RA. A new classification for HIV-1. Nature. 1998 Jan 15;391(6664):240. PubMed PMID: 9440686.

9: Mörner A, Björndal A, Albert J, Kewalramani VN, Littman DR, Inoue R, Thorstensson R, Fenyö EM, Björling E. Primary human immunodeficiency virus type 2 (HIV-2) isolates, like HIV-1 isolates, frequently use CCR5 but show promiscuity in coreceptor usage. J Virol. 1999 Mar;73(3):2343-9. PMID: 9971817.

10: Karlsson I, Antonsson L, Shi Y, Karlsson A, Albert J, Leitner T, Olde B, Owman C, Fenyö EM. HIV biological variability unveiled: frequent isolations and chimeric receptors reveal unprecedented variation of coreceptor use. AIDS. 2003 Dec 5;17(18):2561-9. PubMed PMID: 14685050.

11: Mild M, Esbjörnsson J, Fenyö EM, Medstrand P. Frequent intrapatient recombination between human immunodeficiency virus type 1 R5 and X4 envelopes: implications for coreceptor switch. J Virol. 2007 Apr;81(7):3369-76. Epub 2007 Jan 24. PMID: 17251288.

12. Laurén A, Vödrös D, Thorstensson R, Fenyö EM. Comparative studies on mucosal and intravenous transmission of simian immunodeficiency virus (SIVsm): evolution of coreceptor use varies with pathogenic outcome. J Gen Virol. 2006 Mar;87(Pt 3):581-94. PMID: 16476979.

13: Fenyö EM, Esbjörnsson J, Medstrand P, Jansson M. Human immunodeficiency virus type 1 biological variation and coreceptor use: from concept to clinical significance. J Intern Med. 2011 Dec;270(6):520-31. doi: 10.1111/j.1365-2796.2011.02455.x. Epub 2011 Oct 27. PMID: 21929694.