Frequency of Symptomatic and Asymptomatic Herpes Simplex Virus Type 2 Reactivations among Human Immunodeficiency Virus–Infected Men

Schacker, Timothy W.; Zeh, Judith; Hu, Hui Lin; Hill, Edward C.; Corey, Lawrence

doi:10.1086/314486

Cited by 213 publications

(163 citation statements)

References 29 publications

Supporting

Mentioning

149

Contrasting

Unclassified

Order By: Relevance

“…A clear role for the cellular immune response in controlling HSV reactivation and shedding has been established Posavad et al, 1997Posavad et al, , 1998. HSV is also more frequently shed in human immunodeficiency virus (HIV)-infected individuals with low CD4 + T cell counts (Augenbraun et al, 1995;Schacker et al, 1998). For this reason, dexamethasone immunosuppression was attempted but did not result in the detection of B virus by PCR.…”

Section: Discussionmentioning

confidence: 99%

Differential detection of B virus and rhesus cytomegalovirus in rhesus macaques FN1

Huff

Eberle

Capitanio

et al. 2003

Journal of General Virology

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Differential detection of B virus and rhesus cytomegalovirus in rhesus macaques FN1

Huff

Eberle

Capitanio

et al. 2003

Journal of General Virology

View full text Add to dashboard Cite

“…in the absence of active herpes lesions (12)(13)(14). The frequency of asymptomatic shedding may partially explain why up to 90% of persons with serological evidence of HSV-2 deny any history of herpes symptoms (15).…”

Section: Abstract: Coinfection; Genital Herpes; Hiv; Hsv; Orolabial mentioning

confidence: 99%

“…Higher numbers of target cells likely contribute to the increased HIV susceptibility observed in HSV-2-infected persons. Finally, among individuals who become HSV-2-HIV coinfected, HSV-2 has been associated with increases in HIV viral load in both plasma and genital secretions of up to 0.5 log 10 copies/mL (12,(29)(30)(31)(32), thus increasing the likelihood of secondary HIV transmission to HIV-uninfected partners. Taken together, these findings provide a strong epidemiological and pathophysiological rationale for studying pharmacological HSV-2 suppression as a therapeutic strategy for preventing HIV acquisition.…”

Section: How Hsv-2 May Fuel the Hiv Epidemicmentioning

confidence: 99%

Left out but not Forgotten: Should Closer Attention be Paid to Coinfection with Herpes Simplex Virus Type 1 and HIV?

Tan

Kaul

Walsmley

2009

Canadian Journal of Infectious Diseases and Medical Microbiolog

View full text Add to dashboard Cite

Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are among the most common coinfections seen in individuals infected with HIV-1. Most research on HSV-HIV coinfection has focused on HSV-2, and in particular, on its impact on HIV transmission. HSV-2 is associated with micro- and macroulcerations in genital mucosal surfaces, increased numbers of HIV target cells in genital mucosal tissue and increases in plasma HIV viral load of up to 0.5 log10copies/mL, such that HSV-2 infection increases the risk of both HIV acquisition and transmission. Because plasma HIV RNA levels are a major determinant of rates of CD4 cell decline, HSV-2 coinfection may also adversely affect the progression of HIV disease. Anti-HSV medications have in fact been associated with reciprocal decreases in HIV viral load in short-term studies. These findings have led to the development of several clinical trials of HSV-2 suppression as strategies for preventing HIV transmission and slowing the rate of HIV disease progression. HSV-1 coinfection has largely been ignored from this growing body of research, yet there are several reasons that this coinfection remains an important issue for study. First, the seroprevalence of HSV-1 is consistently higher than that of HSV-2 among both HIV-infected and HIV-uninfected populations, underscoring the relevance of HSV-1 coinfection to the majority of HIV-infected persons. Second, pre-existing HSV-1 antibodies in individuals may modulate the course of subsequently acquired HSV-2 infection; the implications of such changes on HSV-HIV coinfection remain unexplored. Third, HSV-1 and HSV-2 are closely related viruses that share 83% genetic homology. Their virological and pathobiological similarities suggest that their implications on HIV pathogenesis may be similar as well. Finally, HSV-1 is becoming increasingly relevant because the incidence of genital HSV-1 has risen. Although genital herpes is traditionally associated with HSV-2, recent studies have shown that the majority of serologically confirmed primary genital herpes in some settings is attributable to HSV-1. Because the genital tract is an important site of biological interaction between HSV and HIV, this epidemiological change may be clinically important.

show abstract

“…Strong CD8 + responses can be protective in HSV infection-specific mouse models (11). In murine protection models based on attenuated live virus or DNA vaccines, protection is more typically CD4 dependent, and in humans, HSV disease worsens with CD4 depletion in untreated human immunodeficiency virus type 1 (HIV-1) infection (12,13).…”

Section: Introductionmentioning

confidence: 99%

Cross-presentation and genome-wide screening reveal candidate T cells antigens for a herpes simplex virus type 1 vaccine

Jing¹,

Haas²,

Chong³

et al. 2012

J. Clin. Invest.

161

View full text Add to dashboard Cite

Herpes simplex virus type 1 (HSV-1) not only causes painful recurrent oral-labial infections, it can also cause permanent brain damage and blindness. There is currently no HSV-1 vaccine. An effective vaccine must stimulate coordinated T cell responses, but the large size of the genome and the low frequency of HSV-1-specific T cells have hampered the search for the most effective T cell antigens for inclusion in a candidate vaccine. We have now developed what we believe to be novel methods to efficiently generate a genome-wide map of the responsiveness of HSV-1-specific T cells, and demonstrate the applicability of these methods to a second complex microbe, vaccinia virus. We used cross-presentation and CD137 activation-based FACS to enrich for polyclonal CD8 + T effector T cells. The HSV-1 proteome was prepared in a flexible format for analyzing both CD8 + and CD4 + T cells from study participants. Scans with participant-specific panels of artificial APCs identified an oligospecific response in each individual. Parallel CD137-based CD4 + T cell research showed discrete oligospecific recognition of HSV-1 antigens. Unexpectedly, the two HSV-1 proteins not previously considered as vaccine candidates elicited both CD8 + and CD4 + T cell responses in most HSV-1-infected individuals. In this era of microbial genomics, our methods -also demonstrated in principle for vaccinia virus for both CD8 + and CD4 + T cells -should be broadly applicable to the selection of T cell antigens for inclusion in candidate vaccines for many pathogens. IntroductionHerpes simplex virus type 1 (HSV-1) infects 60% of the US population and has a significant cumulative health care burden in addition to causing painful recurrent oral-labial infections. For example, brain and eye infections can cause permanent damage or blindness (1). HSV-1 also causes approximately 50% of clinical first-episode genital herpes in the United States. Vaccines for HSV that have been tested thus far have failed in clinical trials, including a recent phase III trial of an adjuvanted glycoprotein D (gD2) product (2). This vaccine elicits antibody and CD4 + T cell responses but fails to induce CD8 responses. Newer platforms can elicit CD8 + and CD4 + cells, but they require rationally selected T cell antigens. We therefore developed methods to permit measurement of both CD8 and CD4 responses to the complete HSV-1 proteome to begin rational prioritization of next-generation vaccine candidates.Several recent observations support the concept that an effective HSV vaccine will need to induce coordinated CD8 + and CD4 + T cell responses. HSV-1-specific CD8 + T cells localize to the site of HSV-1 infection in human and murine trigeminal ganglia (TG) (3-5), and both HSV-specific CD8 + and CD4 + T cells localize to acute and healed sites of skin infection in mice and humans, sug-

show abstract

Frequency of Symptomatic and Asymptomatic Herpes Simplex Virus Type 2 Reactivations among Human Immunodeficiency Virus–Infected Men

Cited by 213 publications

References 29 publications

Differential detection of B virus and rhesus cytomegalovirus in rhesus macaques FN1

Differential detection of B virus and rhesus cytomegalovirus in rhesus macaques FN1

Left out but not Forgotten: Should Closer Attention be Paid to Coinfection with Herpes Simplex Virus Type 1 and HIV?

Cross-presentation and genome-wide screening reveal candidate T cells antigens for a herpes simplex virus type 1 vaccine

Contact Info

Product

Resources

About