scholarly journals Contribution of Peaks of Virus Load to Simian Immunodeficiency Virus Pathogenesis

2002 ◽  
Vol 76 (5) ◽  
pp. 2573-2578 ◽  
Author(s):  
Roland R. Regoes ◽  
Silvija I. Staprans ◽  
Mark B. Feinberg ◽  
Sebastian Bonhoeffer
Keyword(s):  
Disease Progression ◽  
Simian Immunodeficiency Virus ◽  
Rhesus Macaques ◽  
Equivalent Model ◽  
Time Range ◽  
Survival Times ◽  
Set Point ◽  
Virus Load ◽  
Immunodeficiency Virus ◽  
Viral Load Data

ABSTRACT The mechanisms causing AIDS and subsequently death in human immunodeficiency virus type 1 infection are not yet fully understood. Nonetheless, correlates of accelerated progression to disease based on immunological and virological markers have been identified. The best correlate identified to date is the baseline virus load or the so-called viral set point. By focusing on a virus load measurement from a restricted time range, however, we ignore valuable information contained in the long-term profile of the virus load. Here, we investigate the relationship between virus load and survival with the aid of a statistical model. The model takes into consideration the virus load at every stage of the disease. In particular, we aim to determine the effect of peaks of virus load on disease progression. We fit our model to unique sequential viral load data of 12 simian immunodeficiency virus mac251-infected rhesus macaques which contain frequent measurements throughout the entire course of the infection until the development of simian AIDS. Our model enables us to predict the survival times of the animals more accurately than an equivalent model which considers the viral set point only. Furthermore, we find that peaks of the virus load contribute less to disease progression than phases of low virus load with the same amount of viral turnover. Our analysis implies that the total viral turnover is not the best correlate of survival. As a consequence, the direct cytopathic effects of virus replication may, by themselves, have less of an impact on disease progression than previously thought.

scholarly journals Control of Simian Immunodeficiency Virus SIVmac239 Is Not Predicted by Inheritance of Mamu-B*17-Containing Haplotypes

2006 ◽  
Vol 81 (1) ◽  
pp. 406-410 ◽  
Author(s):  
Jason A. Wojcechowskyj ◽  
Levi J. Yant ◽  
Roger W. Wiseman ◽  
Shelby L. O'Connor ◽  
David H. O'Connor
Keyword(s):  
Human Immunodeficiency Virus ◽  
Disease Progression ◽  
Simian Immunodeficiency Virus ◽  
Virus Disease ◽  
Rhesus Macaques ◽  
Host Genetics ◽  
Mhc Genes ◽  
Histocompatibility Complex ◽  
Identical By Descent ◽  
Immunodeficiency Virus

ABSTRACT It is well established that host genetics, especially major histocompatibility complex (MHC) genes, are important determinants of human immunodeficiency virus disease progression. Studies with simian immunodeficiency virus (SIV)-infected Indian rhesus macaques have associated Mamu-B*17 with control of virus replication. Using microsatellite haplotyping of the 5-Mb MHC region, we compared disease progression among SIVmac239-infected Indian rhesus macaques that possess Mamu-B*17-containing MHC haplotypes that are identical by descent. We discovered that SIV-infected animals possessing identical Mamu-B*17-containing haplotypes had widely divergent disease courses. Our results demonstrate that the inheritance of a particular Mamu-B*17-containing haplotype is not sufficient to predict SIV disease outcome.

scholarly journals Chronic Δ9-Tetrahydrocannabinol Administration May Not Attenuate Simian Immunodeficiency Virus Disease Progression in Female Rhesus Macaques

2014 ◽  
Vol 30 (12) ◽  
pp. 1216-1225 ◽  
Author(s):  
Angela M. Amedee ◽  
Whitney A. Nichols ◽  
Nicole J. LeCapitaine ◽  
Curtis Vande Stouwe ◽  
Leslie L. Birke ◽  
...  
Keyword(s):  
Disease Progression ◽  
Simian Immunodeficiency Virus ◽  
Virus Disease ◽  
Rhesus Macaques ◽  
Immunodeficiency Virus ◽  
Female Rhesus ◽  
Female Rhesus Macaques

scholarly journals Viral Dynamics during Primary Simian Immunodeficiency Virus Infection: Effect of Time-Dependent Virus Infectivity

2010 ◽  
Vol 84 (9) ◽  
pp. 4302-4310 ◽  
Author(s):  
Naveen K. Vaidya ◽  
Ruy M. Ribeiro ◽  
Christopher J. Miller ◽  
Alan S. Perelson
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Average Rate ◽  
Acute Infection ◽  
Time Dependent ◽  
Virus Infectivity ◽  
Plasma Virus ◽  
Set Point ◽  
Immunodeficiency Virus ◽  
Viral Load Data ◽  
Intravenous Inoculation

ABSTRACT A recent experiment involving simian immunodeficiency virus (SIV) infection of macaques revealed that the infectivity of this virus decreased over the first few months of infection. Based on this observation, we introduce a viral dynamic model in which viral infectivity varies over time. The model is fit to viral load data from eight (donor) monkeys infected by intravaginal inoculation of SIVmac251, three monkeys infected by intravenous inoculation of virus isolated from the donors during the ramp-up phase of acute infection, and three monkeys infected by intravenous inoculation of virus isolated at the viral set-point. Although we only analyze data from 14 monkeys, the new model with time-dependent infectivity seems to fit the data significantly better than a widely used model with constant infectivity (P = 2.44 × 10−11). Our results indicate that plasma virus infectivity on average decays ∼8-fold (95% confidence interval [CI] = 5.1 to 10.3) over the course of acute infection, with the decay occurring exponentially with an average rate of 0.28 day−1 (95% CI = 0.14 to 0.42 day−1). The decay rate in set point plasma virus recipient animals is ∼16 times slower than in ramp-up plasma virus recipient animals and ∼6 times slower than in donor animals. Throughout acute infection up to the set-point, the infection rate is higher in ramp-up plasma virus recipient animals than in set-point plasma virus recipient animals. These results show that the infectivity depends upon the source of viral infection.

scholarly journals Host factors determine differential disease progression after infection with nef-deleted simian immunodeficiency virus

2014 ◽  
Vol 95 (10) ◽  
pp. 2273-2284 ◽  
Author(s):  
Sieghart Sopper ◽  
Kerstin Mätz-Rensing ◽  
Thorsten Mühl ◽  
Jonathan Heeney ◽  
Christiane Stahl-Hennig ◽  
...  
Keyword(s):  
Viral Load ◽  
Viral Replication ◽  
Disease Progression ◽  
Simian Immunodeficiency Virus ◽  
Mhc Class Ii ◽  
Cell Activation ◽  
Host Factors ◽  
Immunological Parameters ◽  
Set Point ◽  
Immunodeficiency Virus

Infection of macaques with live attenuated simian immunodeficiency virus (SIV) usually results in long-lasting efficient protection against infection with pathogenic immunodeficiency viruses. However, attenuation by deletion of regulatory genes such as nef is not complete, leading to a high viral load and fatal disease in some animals. To characterize immunological parameters and polymorphic host factors, we studied 17 rhesus macaques infected with attenuated SIVmac239ΔNU. Eight animals were able to control viral replication, whereas the remaining animals (non-controllers) displayed variable set-point viral loads. Peak viral load at 2 weeks post-infection (p.i.) correlated significantly with set-point viral load (P<0.0001). CD4+ T-cell frequencies differed significantly soon after infection between controllers and non-controllers. Abnormal B-cell activation previously ascribed to Nef function could already be observed in non-controllers 8 weeks after infection despite the absence of Nef. Two non-controllers developed an AIDS-like disease within 102 weeks p.i. Virus from these animals transmitted to naïve animals replicated at low levels and the recipients did not develop immunodeficiency. This suggested that host factors determined differential viral load and subsequent disease course. Known Mhc class I alleles associated with disease progression in SIV WT infection only marginally influenced the viral load in Δnef-infected animals. Protection from SIVmac251 was associated with homozygosity for MHC class II in conjunction with a TLR7 polymorphism and showed a trend with initial viral replication. We speculated that host factors whose effects were usually masked by Nef were responsible for the different disease courses in individual animals upon infection with nef-deleted viruses.

scholarly journals Mucosal Innate Immune Response Associated with a Timely Humoral Immune Response and Slower Disease Progression after Oral Transmission of Simian Immunodeficiency Virus to Rhesus Macaques

2007 ◽  
Vol 81 (12) ◽  
pp. 6175-6186 ◽  
Author(s):  
Jeffrey M. Milush ◽  
Kelly Stefano-Cole ◽  
Kimberli Schmidt ◽  
Andre Durudas ◽  
Ivona Pandrea ◽  
...  
Keyword(s):  
Immune Response ◽  
Disease Progression ◽  
Simian Immunodeficiency Virus ◽  
Rhesus Macaques ◽  
Interferon Response ◽  
Mrna Levels ◽  
Oligoadenylate Synthetase ◽  
Mucosal Transmission ◽  
Immunodeficiency Virus ◽  
Innate Effector

ABSTRACT Mucosal transmission is the predominant mode of human immunodeficiency virus (HIV) infection worldwide, and the mucosal innate interferon response represents an important component of the earliest host response to the infection. Our goal here was to assess the changes in mRNA expression of innate mucosal genes after oral simian immunodeficiency virus (SIV) inoculation of rhesus macaques (Macaca mulatta) that were followed throughout their course of disease progression. The SIV plasma viral load was highest in the macaque that progressed rapidly to simian AIDS (99 days) and lowest in the macaque that progressed more slowly (>700 days). The mRNA levels of six innate/effector genes in the oral mucosa indicated that slower disease progression was associated with increased expression of these genes. This distinction was most evident when comparing the slowest-progressing macaque to the intermediate and rapid progressors. Expression levels of alpha and gamma interferons, the antiviral interferon-stimulated gene product 2′-5′ oligoadenylate synthetase (OAS), and the chemokines CXCL9 and CXCL10 in the slow progressor were elevated at each of the three oral mucosal biopsy time points examined (day 2 to 4, 14 to 21, and day 70 postinfection). In contrast, the more rapidly progressing macaques demonstrated elevated levels of these cytokine/chemokine mRNA at lymph nodes, coincident with decreased levels at the mucosal sites, and a decreased ability to elicit an effective anti-SIV antibody response. These data provide evidence that a robust mucosal innate/effector immune response is beneficial following lentiviral exposure; however, it is likely that the anatomical location and timing of the response need to be coordinated to permit an effective immune response able to delay progression to simian AIDS.

scholarly journals Factors Associated with Slow Disease Progression in Macaques Immunized with an Adenovirus-Simian Immunodeficiency Virus (SIV) Envelope Priming-gp120 Boosting Regimen and Challenged Vaginally with SIVmac251

1999 ◽  
Vol 73 (9) ◽  
pp. 7430-7440 ◽  
Author(s):  
Suzan L. Buge ◽  
Lalita Murty ◽  
Kamalpreet Arora ◽  
V. S. Kalyanaraman ◽  
Phillip D. Markham ◽  
...  
Keyword(s):  
Immune Responses ◽  
Disease Progression ◽  
Simian Immunodeficiency Virus ◽  
Rhesus Macaques ◽  
Viral Envelope ◽  
Virus Envelope ◽  
Partial Protection ◽  
Vaccine Regimen ◽  
Cd4 Counts ◽  
Immunodeficiency Virus

ABSTRACT Rhesus macaques were immunized with a combination vaccine regimen consisting of adenovirus type 5 host range mutant-simian immunodeficiency virus envelope (Ad5hr-SIVenv) recombinant priming and boosting with native SIV gp120. Upon intravaginal challenge with SIVmac251, both persistently and transiently viremic animals were observed (S. L. Buge, E. Richardson, S. Alipanah, P. Markham, S. Cheng, N. Kalyan, C. J. Miller, M. Lubeck, S. Udem, J. Eldridge, and M. Robert-Guroff, J. Virol. 71:8531–8541, 1997). Long-term follow-up of the persistently viremic immunized macaques, which displayed significantly reduced viral burdens during the first 18 weeks postchallenge compared to controls, has now shown that one of four became a slow progressor, clearing virus from plasma and remaining asymptomatic with stable CD4 counts for 134 weeks postchallenge. Reboosting of the transiently viremic macaques did not reactivate latent virus. Rechallenge with two sequential SIVmac251 intravaginal exposures again resulted in partial protection of one of two immunized macaques, manifested by viral clearance and stable CD4 counts. No single immune parameter was associated with partial protection. Development of a strong antibody response capable of neutralizing a primary SIVmac251 isolate together with SIV-specific cytotoxic T lymphocytes were implicated, while CD8+ T-cell antiviral activity and mucosal immune responses were not associated with delayed disease progression. Our data show that even a third immunization with the same Ad5hr-SIVenv recombinant can elicit significant immune responses to the inserted gene product, suggesting that preexisting Ad antibodies may not preclude effective immunization. Further, the partial protection against a virulent, pathogenic SIV challenge observed in two of six macaques immunized with a vaccine regimen based solely on the viral envelope indicates that this vectored-vaccine approach has promise and that multicomponent vaccines based in the same system merit further investigation.

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