Hongshuo Song, PhD

Education and Training:

2002-2007: Bachelor of Medicine (MD equivalent), Peking University

2007-2010: PhD, Peking University (thesis advisor: Prof. Hui Zhuang)

2010-2015: Postdoctoral Associate, Duke University  

The research in my laboratory focuses on the interface of HIV genetic evolution, phenotypic property and pathogenesis. We combine conventional approaches in virology and novel technologies such as next-generation sequencing to address fundamental questions relevant to HIV treatment and prevention. We are particularly interested in the following areas:

The "escape by shifting" concept: virus entry pathway alteration as an evolutionary mechanism of immune evasion. Virus entry pathway, largely governed by receptor specificity, is a major determinant for cellular and tissue tropism, pathogenesis, and host range. The fast-evolving nature and high genetic plasticity confer receptor flexibility on many viruses, from bacteriophage to those infecting humans. Alteration in receptor specificity could be closely related with viral pathogenesis, such as the process of “coreceptor switch” in HIV infection that is associated with faster progression to AIDS, and may contribute to host-jumping, as exemplified by coronavirus and influenza virus. However, the molecular mechanisms underlying viral receptor usage alteration is a fundamental gap in knowledge. Recent studies of our group elucidated the evolutionary process of coreceptor switch in natural HIV infection. The findings demonstrate that “driver mutations” responsible for coreceptor switch can confer complete escape to V3 broadly neutralizing antibodies. These observations, together with the fact that the receptor binding regions of many viruses overlap with antigenic epitopes, prompted us to propose a novel concept termed “escape by shifting”. The central hypothesis is that for viruses with entry pathway flexibility, entry pathway alteration can function as an evolutionary mechanism of immune evasion. We coin the term “receptor utilization space” to describe the repertoire of receptors that can be used by a particular virus. Under immune pressure, a virus explores its “receptor utilization space” while exploring the sequence space and fitness landscape. Immune escape mutations and compensatory mutations could both confer novel receptor usage, which functions as a mechanism to maintain virus entry capacity while evading host immune recognition. We are trying to decipher the molecular mechanisms of virus entry pathway alteration under host immune pressure by using HIV-1 and SARS-CoV2 as models (supported by NIH grant R01AI181601). 

The global phenotypic diversity of HIV-1. The extensive genetic diversity of HIV-1 in the global epidemic has been well demonstrated. However, how such genetic-level variation translates into diverse phenotypic traits, and in turn influences the outcomes of the disease and treatment and prevention strategies remains poorly understood. One of our long-term goals is to better characterize the global phenotypic diversity of HIV-1. The motivation comes from our recent observation that distinct phylogenetic clusters within the same clade can have different CD4 virulence (Song et.al, PNAS, 2019). We hope the knowledge obtained can help to more precisely inform therapeutic and preventative approaches in different regions of the world where distinct HIV-1 subtypes/CRFs predominate.

Role of HIV fitness in viral load rebound dynamics. An important goal in HIV vaccine development is to target highly conserved epitopes with high fitness constraint. In collaboration with the US Military HIV Research Program (MHRP), we will investigate the correlation between HIV replication fitness and the dynamics of viral load rebound in a therapeutic vaccine trial among acutely treated individuals (RV405). The long-term goal is to translate knowledge of HIV vulnerabilities into optimizing future vaccine strategies towards the goal of ART-free remission.

Our major collaborators include scientists from the U.S. Military HIV Research Program, Duke University and the Los Alamos National Laboratory.

We are currently inviting highly motivated individuals to join the team at the levels of postdoctoral fellow, graduate student, and research assistant (please contact Dr. Song at: hongshuo.song@ihv.umaryland.edu). 

Molecular virology, HIV, Viral fitness, Coreceptor switching, Evolution dynamics, Therapeutic vaccine

Marichannegowda MH, Zemil M, Wieczorek L, Sanders-Buell E, Bose M, O'Sullivan AM, King D, Francisco L, Diaz-Mendez F, Setua S, Chomont N, Phanuphak N, Ananworanich J, Hsu D, Vasan S, Michael NL, Eller LA, Tovanabutra S, Tagaya Y, Robb ML, Polonis VR, Song H. Tracking coreceptor switch of the transmitted/founder HIV-1 identifies co-evolution of HIV-1 antigenicity, coreceptor usage and CD4 subset targeting: The RV217 acute infection cohort study. EBioMedicine. 2023 Dec;98:104867.

Marichannegowda MH, Song H. Immune escape mutations selected by neutralizing antibodies in natural HIV-1 infection can alter coreceptor usage repertoire of the transmitted/founder virus. Virology. 2022 Mar;568:72-76.

Colby DJ,  Sarnecki M, Barouch DH, Tipsuk S, Stieh DJ, Kroon E, Schuetz A, Intasan J, Sacdalan C, Pinyakorn S, Grandin P, Song H, Tovanabutra S, Shubin Z, Kim D, Paquin-Proulx D, Eller MA, Thomas R, Souza M, Wieczorek L, Polonis VR, Pagliuzza A, Chomont N, Peter L, Nkolola JP, Vingerhoets J, Truyers C, Pau MG, Schuitemaker H, Phanuphak N, Michael NL, Robb ML, Tomaka FL, Ananworanich J and the HTX1001/RV405 Study Team. Safety and Immunogenicity of Ad26, MVA vaccines in acutely treated HIV and effect on viral rebound after ART interruption. Nature Medicine. 26(4):498-501. 2020. 

Song H, Ou W, Feng Y, Zhang J, Li F, Hu J, Peng H, Xing H, Ma L, Tan Q, Li D, Wang L, Wu B, Shao Y. Disparate impact on CD4 T cell count by two distinct HIV-1 phylogenetic clusters from the same clade. Proc Natl Acad Sci U S A. 116(1):239-244. 2019.

Song H*, Giorgi EE*, Ganusov VV, Cai F, Athreya G, Yoon H, Carja O, Hora B, Hraber P, Romero-Severson E, Jiang C, Li X, Wang S, Li H, Salazar-Gonzalez JF, Salazar MG, Goonetilleke N, Keele BF, Montefiori DC, Cohen MS, Shaw GM, Hahn BH, McMichael AJ, Haynes BF, Korber BT, Bhattacharya T, Gao F. Tracking HIV-1 recombination to resolve its contribution to HIV-1 evolution in natural infection. Nature Communications. 9(1):1928. 2018 (*equal contribution).