Manish Sagar, MD

Assistant Professor of Medicine

Section of Retroviral Therapeutics
Brigham and Women’s Hospital
65 Landsdowne Street, Room 415
Cambridge, MA 02139
Phone: (617) 768-8372
Fax:(617) 768-8738
Email: msagar@partners.org
2 Postdoc, 1 graduate student

The major interests of the laboratory are in understanding the pathogenesis of HIV-1 transmission. It has been shown that from a chronically infected host with a wide variety of viruses, only a small number of variants are transmitted to a newly infected subject. Transmission does not occur in a random manner, but rather specific variants are selected for transmission. We are working on deciphering the viral genotypes and phenotypes that are selected during transmission. We have defined sequences in the virus envelope gene that are associated with viruses found early after heterosexual transmission. We are examining whether these signature envelope genotypes are also selectively chosen during other forms of HIV-1 transmission. In addition, we are beginning to examine how the specific envelope sequences found early in infection confer an advantage during transmission. These studies will increase our understanding of early host cell-virus interactions, which will help in the designing rational strategies to prevent HIV-1 transmission.

Hepatitis GB-C virus (GBV-C) is another active area of investigation in the lab. Hepatitis GBV-C is not associated with any known human disease. It can persist for prolonged periods after infection. Interestingly, active hepatitis GBV-C co-infection has been associated with a significantly delayed HIV-1 disease progression. We are actively developing recombinant hepatitis GBV-C to understand viral pathogenesis and examine its potential use for antigen delivery.

References:

Tsibris A, Sagar M, Gulick R, Su Z, Hughes M, Greaves W, Subramanian M, Flexner C, Leopold K, Coakley E, Kuritzkes D. The in vivo emergence of vicriviroc resistance in an HIV-1 subtype C infected subject. Journal of Virology. 82 (16): 8210-8214, 2008. 

Sagar M, Laeyendecker O, Lee S, Gamiel J, Wawer MJ, Gray RH, Serwadda D, Sewankambo NK, Shepherd JC, Toma J, Huang W, Quinn TC.  HIVs with signature genotypic characteristics are selected during heterosexual transmission. Journal of Infectious Diseases.  199: 580-9, 2009.

Paredes R, Sagar M, Marconi VC, Hoh R, Martin JN, Parkin NT, Petropoulos CJ,  Deeks SG, Kuritzkes DR. Mechanisms of slow decay of multidrug resistant HIV-1 carrying the M184V mutation in viremic subjects interrupting reverse transcriptase inhibitors.  Journal of Virology. 83 (4): 2038-43, 2009

Sagar M, Lavreys L, Baeten JM, Richardson BA, Mandaliya K, Chohan BH, Kreiss JK, Overbaugh J. Infection with multiple HIV-1 variants is associated with faster disease progression. J Virol 2003;77(23):12921-6.

Sagar M, Lavreys L, Baeten JM, Richardson BA, Mandaliya K, Achola N, Kreiss JK, Overbaugh J. Identification of modifiable factors that affect the genetic diversity of the transmitted HIV-1 population. AIDS 2004;18:615-619.

Sagar M, Kirkegaard E, Long EM, Celum C, Buchbinder S, Daar ES, Overbaugh J. HIV-1 diversity at the time of infection is not restricted to certain populations or specific HIV-1 subtypes. J Virol 2004;78(13):7279-7283.

Chohan B*, Lang D*, Sagar M*, Korber B, Lavreys L, Richardson B, Overbaugh J. Selection for HIV-1 envelope glycosylation variants during transmission J Virol 2005; 79 (10) 6528-6531

*authors contributed equally to this work

Sagar M, Kirkegaard E, Lavreys L, Overbaugh J. Diversity in HIV-1 envelope V1-V3 sequences early in infection reflects sequence diversity throughout the HIV-1 genome but does not predict the extent of sequence diversity during chronic infection. AIDS Research and Human Retroviruses. 22.5:430-437, 2006.

Sagar M, Wu X, Lee S, Overbaugh J. HIV-1 V1-V2 envelope loop sequences expand and add glycosylation sites over the course of infection and these modification affect antibody neutralization sensitivity. Journal of Virology. 80 (19):9586-98, 2006.